There's a decent amount of cynicism in the comments, which I understand. I think this is a really cool and novel study, though.
Historically, cancer was treated with therapies that are toxic to all cells, relying on the fact that cancer cells divide quickly and are unable to handle stress as well as normal cells (chemotherapy, radiation).
The last couple of decades we've seen many targeted cancer therapies. These drugs generally inhibit the activity of a specific protein that lets the cancer cells grow (e.g. EGFR inhibitors) or prevents the immune system from killing the cancer cells (e.g. PDL1 inhibitors).
This mechanism is way more interesting. The gene BCL6 is usually turned on in immune cells when they are mutating to recognize foreign invaders. This process involves lots of DNA damage and stress, but BCL6 stops the cells from dying and is therefore important for normal immune function. Unfortunately, this makes BCL6 a gene that is often co-opted in cancer cells to help them survive.
The method cleverly exploits the oncogenic function of BCL6 not by inhibiting it, but by turning it into a guide, enabling the delivery of activating machinery to the targets of BCL6 and reversing the inhibitory effects on cell death.
The whole field of targeted degraders, molecular glues, and heterobifunctional molecules is a growing area of interest in cancer research.
This comment hits the nail on the head. Another big consideration with the technology in this paper that hasn't been mentioned in this thread is that it opens up a huge range of possibilities for targeting "undruggable" protein targets. Most drugs are small molecules that bind to sites an (relatively much larger) proteins, thereby getting in the way of their function. Unfortunately the vast majority of proteins do not have a site that can be bound by a molecule in a way that 1) has high affinity, 2) has high specificity (doesn't bind to other proteins) and 3) actually abolishes the protein's activity.
With "induced proximity" approaches like the one in this study, all you need is a molecule that binds the target protein somewhere. This idea has been validated extensively in the field of "targeted protein degradation", where a target protein and an E3 ubiquitin ligase, a protein that recruits the cell's native proteolysis machinery, are recruited to each other. The target protein doesn't have to be inactivated by the therapeutic molecule because the proteolysis machinery destroys it, so requirement #3 from above is effectively removed.
The molecule in this study does something similar to targeted protein degradation, but this time using a protein that effects gene expression instead of one that recruits proteolysis machinery. The article focuses on the fact that cancers are addicted to BCL6. This is an important innovation in the study and an active area of research (another example at [1]), but leaves out the fact that these induced proximity platforms are much more generalizable than traditional small molecules because it's the proteins that they recruit that do all the work rather than the molecules themselves. This study goes a long way to validate this principle, pioneered by targeted protein degradation and PROTACs, and shows that it can be applied broadly.
I haven’t read the paper yet but the news article seemed a bit, meeh.
BCL-2 inhibitors, mainly Venetoclax, is used in cancer therapies quite often which also triggers cell apoptosis and it’s very effective. It was also designed to target B-cell related cancers, but it found to be so effective that FDA approved it to be used in primary cases of Acute Myeloid Leukemia. So, killing cancer with triggerring apoptosis is very well known. I think the novel part might be the two protein, so it is probably more targeted for metabolic activities… but yeah didn’t read the paper yet.
Anyways, for the side effects a major one could be Tumor Lysis Syndrome (TLS). Basically, if you apoptose the cancer cells super fast, the molecules from those cells spread everywhere and it becomes toxic for the patient. This is at least the case for Venetoclax.
Cancerous cells are fairly diverse across individuals, or even within a single individual, and many biological treatments require precise sequencing of the tumor DNA of that individual patient to adjust and work. In some cancers, there is a nasty "Russian roulette" effect in play, where a certain treatment may be extremely efficient (in practice a cure, even though oncologists avoid that word) in people with a certain mutation and totally useless in others, even though from the macroscopic point of view, their tumors look the same.
Then, basically, each cancer, cancer cells should be sequenced, then based on the type of cell and DNA sequencing, we have a list of "tools" to deliver payload to those very cells (without delivering such payload to sane cells, ofc)?
In practice, we can only make use of some known mutations. Not just for delivering chemicals, but also for "teaching" the immune system to attack such cells, which, once it is able to recognize them, it will do vigorously.
Let's hope that this catalogue will grow until it covers at least all the typical cases.
My understanding is that even though immunotherapy's mechanism may seem more natural than chemotherapy and radiation, and in some instances may be a magic bullet, up-regulating the immune system can have serious consequences. I remember reading about a clinical trial showing similar progression free survival but increased grade 4-5 toxicities (requiring hospitalization or being fatal). My assumption was that these are autoimmune conditions that are aggravated in some of the patient population.
oop talked about mechanism, so we can't know side effects here. someone will publish a new drug that relies on this mechanism, and then they will check the side effects of the specific drug on cells, rats, or other experimental species.
All of this stuff is promising, and I hope the diagnostic side catches up as well.
Just went to a funeral this weekend for a 40 year old who died of breast cancer 4 weeks after diagnosis at her first annual mammogram.
A lot of skeptical people under 30 here haven't lived through regularly various cancer diagnoses in their friends & family group that your late 30s/early 40s starts to bring.
I don't have the data on it, but anecdotally I notice that women's cancers seem to strike 5-10 years earlier than mens even if they can be caught early & treated well.. Though apparently men have overall worse cancer survival rates.
I'm finishing my PhD in hyperpolarization (hopefully) soon. In my opinion, hyperpolarization will significantly contribute to early-stage diagnosis. We're designing machines, processes, and chemicals that create novel contrast agents for MRI, enabling the localization of cancer cells and even tracking their metabolism. For example, it's possible to inject hyperpolarized pyruvate and track its conversion to lactate. Essentially, this technique boosts the MRI/NMR signal of the contrast agent by up to 100,000-fold. When the contrast agent undergoes metabolism, it creates a unique signal footprint through chemical shift changes, which can aid in characterizing cancer.
I have a question, if you don't mind. What are the nuclei polarized relative to? The molecules in a liquite rotate a lot and I am curious whether the nuclear spins stay aligned with the electron systems or if they remain fixed in an inertial frame.
There are two semi-connected concepts at play here. Polarization in this context refers to the ratio of neutralizing (i.e. "up" vs "down") spins in a given system. For most nuclei in organic systems like protons, carbons, and nitrogens, this ratio is naturally very small, which is the reason that magnetic resonance approaches like MRI usually have poor signal-to-noise. Hyperpolarization techniques usually involve the transfer of polarization from a source of high ratio, like a free electron, to a relevant target (in the original poster's example, 13C in pyruvate). The polarization in this case is hyperpolarized 13C, which has an "up"-to-"down" spin ratio that is much higher than regular 13C, which makes the signal-to-noise that you get from the pyruvate much higher than it would be otherwise. Tumors love pyruvate so this approach means that tumors will light up like a beacon in your MRI.
The physical rotation/tumbling of molecules in an MRI is also very important, because the strong magnetic field is the thing inducing the "up"-vs-"down" split in the first place, and if the molecular motion is happening at a certain frequency with respect to the external magnetic field there are other interactions that can come into play which can affect the coherence of the nuclear spins (i.e. they can fall out of sync). Thankfully, the rotation of a small molecule like pyruvate is very fast (might higher then the "spin" frequency-a.k.a the Larmor frequenct of 13C at the magnetic field strengths involved in MRI) so the physical tumbling of pyruvate doesn't really come into play when trying to measure its signal. It can be another story for molecules that don't tumble quickly, like the ones that make up tissues, fat, etc.
Great explanation. Indeed, the "rotation/tumbling" is nothing to worry about. One of our biggest challenges is relaxation. The moment we polarize, the clock ticks. Usually, the time scope is around 15-90s. I'm in the field of para-hydrogen and built automated systems which carry out the chemical reactions, polarization transfers and sample cleaning. Many hyperpolarization experiments with para-hydrogen prefer nasty solvents as chloroform or methanol. It is a technical challenge to replace them by water within seconds. One of my favorite topics is Xenon hyperpolarization. It's very elegant, no cleaning required, no wet chemistry, and provides amazing lung scans.
Sounds exciting. Routine periodic medical imaging seems like one of those Star Trek technologies thats in reach but not quite been implemented outside of rich countries in Asia.
Hyperpolarization also allows for cheaper MRI scanners. With hyperpolarization, you achieve polarization (needed for SNR) without the need of big magnets (=expensive). Even in rich countries, MRI scanners reach their physical and technical limits. 3T magnets are already 7-figures and costs of bigger magnets will increase non-linearly. Moreover, with higher fields, side effects increase, too.
We were surprised, but it happens. Breast cancer can be very fast moving.
Unless they have family history, women aren't told to do annual exams until you hit 40.
The symptoms may not be too specific or startling even when it is into stages 3 & 4.
Worth reminding the women in your lives to check their family history and consider getting early exams either way. A lot of times it turns out women do have family history that went undiscussed until they ask mom, aunts, grandmothers, etc.
The other cancers that worry me are the slow moving imperceptible symptomless ones like pancreatic, liver, kidney, etc. Know a few people who around 50 discovered they had stage 2-3 cases due to unrelated scans they got from an accident injury. Some of these you have 5-10+ years window to treat it and live without impact to lifespan.. but most people don't catch it until stage 4 when they actually feel sick and it is too late.
Some people die by cancer, other overcome the cancer, and a small amount don't stand the treatment and die by the chemotherapy. Sometimes by genetics, and can't always be known before. It also depends on how much advanced and aggressive is the tumor.
I believe I read, but can't find the source now, that the sex-specific survival rate is mostly explained by men not catching it and starting treatment as early as women.
Even for cancers that shouldn't be sex-specific, like lung cancer, men are less likely to survive it.
Same as mountainriver's comment. I really find strange how I've been reading news lines over the past years about great advancements in many incurable and chronic diseases (like Alzheimer's, diabetes, and cancers) yet after all that time people's treatment is not going any better. I'm not sure whether scientific journalism somehow delivered some unintended messages to me, or we're just supposed to experience these great advancements after couple of decades from the announcement.
HIV has gone from death sentence to completely preventable with a single daily pill or every 6 months injection, and readily treatable to the point where we have geriatric HIV patients. Obesity is now effectively treatable even taking into account compliance. Hep C can be cured entirely with just six months of oral medication rather than a barely tolerable intravenous course that didn't work all that well. These are massive improvements that have changed how hundreds of millions of people are treated and their prognosis.
The road to the clinic is long, but there have been very big improvements.
And stage 4 melanoma used to mean you'd be dead in a year. I know someone who got diagnosed with it almost a decade ago, got three doses of immunotherapy, and is now cancer-free. Doesn't even have to get scans anymore.
Melanoma is the main cancer that responds well to immunotherapy, PD-1 inhibitors. Other solid cancers, not so much, although in combination with other therapies, is seeing some okay results.
They recently found some types of rectal cancer to be PD-1 sensitive.
Two things. If you follow the news closely, but lack specific expertise or knowledge, you develop this nihilistic sense of doom to some degree. The narrative of our age is that everything is in decline. It pulls clicks.
The other thing is that cancers are not created equal, not all treatments are evolving quickly. Your loved one may be suffering, and that’s your world.
I will say that I lost my beautiful wife a little over a year ago. She had an aggressive cancer, for which the 10-year survival rate was zero. Thanks to the miracle of immunotherapy, the five year survival rate is about 65%. At the same time, my 78 year old aunt successfully fought lung cancer that was a death sentence 20 years ago.
As far as I understand it these immunotherapies are tailor-made to the very specific cancer and its genetics that a patient has, which is also why the stuff is so darn expensive. So you can't have a vaccine until you already have the cancer.
And as always, when problems get solved, other problems get revealed. We didn't even really know about cancer until life expectancies got to the point where dying in your 30s is a tragedy instead of being fairly normal.
I don’t think dying in your 30s has been normal in the Western world anytime In the last 500 years. Remember all those life expectancy mean statistics were heavily dragged down by the huge infant mortality stats.
If your comment was more talking about the Stone Age or something, I apologize for misinterpreting :)
The idea that most people more than ~120 years ago died in their 30s or 40s is a popular misconception. LEAB (Life expectancy at birth) used to be in the mid-30s, but this was largely due to a bimodal distribution of deaths: a large number dying during childbirth, infancy, or early childhood, and a lot at more typical old age (60-70, still a bit lower than is common in much of the west today, but you get the idea). If you made it past puberty, there were pretty good odds of you making it to old age.
100%. I carried this misconception after high school and college and was surprised to learn it’s completely wrong. There’s a name for the old-age end of the bimodal distribution: longevity. Longevity is the natural lifespan of people who don’t die of any early mortality factors. Most people who have the misconception are accidentally conflating life expectancy with longevity. A few unscrupulous peddlers of false hope, like Ray Kurzweil for example, intentionally conflate life expectancy with longevity to reinforce the misconception. As I was learning about longevity I started talking to my anthropologist brother about it, and he was like, oh yeah, people who don’t die from war or disease or infection have always lived to be about 80 years old for all of known history. He mentioned there’s plenty of written evidence from, e.g. Socrates’ day, and also lots of human remains that support it from ten thousand years ago.
This is why life expectancy has gone up, while longevity has mostly remained unchanged (for at least thousands of years). Longevity represents the best we can do, and life expectancy can’t exceed longevity. Life expectancy will asymptotically approach longevity as medicine improves.
I think it's worth noting that we (in the west) have a lot less of most diseases and infections now, stuff like polio, plague, malaria.
I don't suffer from delusions that we have accurate data on conditions like obesity and T2D going back to the middle ages, but we have seen incidence rates of these kinds of disease explode upwards over the last century.
I'd be interested in more detailed data broken down by disease over time.
10ish years ago Myleoma was a semi death sentence, it’s now coming close to being treated like a chronic condition. There are definitely improvements happening, but we’ll often miss them because it’s incremental rather than “we developed this cure for lung cancer and it’s no longer a problem”
Edit: some of the replies below are pretty bleak “it’s just a few months that’s nothing”. The difference between a 5 year and 15 year life expectancy for a parent being diagnosed with blood cancer around 60 is huge.
I am curious: why would it make a difference for a 60 year old if they are a parent and have 5 or 15 years vs not?
I would have thought by that age children are long independent...
Exactly - in my father's case would be difference between dying before all your kids marry vs meeting all your grandkids, helping to watch them.. and seeing them grow up and start going to school.
It's the articles that decry "Big discovery in X".
This could be because the researchers need funding so they will hype the results as much as possible.
Then the articles need as much readership so the journalists hype the results as much as possible.
Then the people suffering from the disease want as much help as possible so they push the articles/papers to the doctors.
On the other hand, it's been my experience that GLP-1 agonsists weren't overhyped, I was completely surprised when my doctor prescribed Mounjaro for weight loss. Even after decades of articles about "NEW WEIGHT LOSS TREATMENT!" (See
also phen-phen)
If you stop believing the bullshit headlines you will see that newer treatments simply increase OS by a few months and that's sufficient to claim significant improvement. In terms of patient outcomes, not a major difference, the cancer still kills you in the end. it's just KPI hacking.
Long term remission is just a few months extra to live. In the end you have people who die quickly and people that live for years. That's why you get averages of a few months extra.
Cancer detection/testing has gotten a lot more attention. Detected early, many victims are still alive after 5 years and considered "cured." But it still gets you in the end. A lot of expense and misery while under medication/chemo/rad/surgical therapy and in the end you are dead just the same.
I'm not sure why this matters. In the end we're all going to die, death is inescapable. The ultimate form of your rationalization is that we should simply not treat anything because we die all the same.
But for many cancers and other diseases not only has early detection gotten better but so has treatment and prognosis. Treatment isn't nearly as bad to go through and long term survival rates are higher. People can live longer with cancer while still being fully functioning.
Each medical innovation overcomes but one hurdle on a path to a treatment/cure, often revealing new hurdles that weren't visible (or important) until the first hurdle fell.
A good example is lipid nanoparticles, which for the first 15 years or more of their existence were horrifically lethal in every hominid, making their potential for delivering transformative genetic or immune cargo into cells impossible. Finally, PEGylation was introduced into their formulation, bypassing the toxic effect they had in precipitating out nearly all of each animal's platelets upon treatment. Within just a few years, LNPs became a very effective way to deliver MRNA vaccines to BILLIONS of human patients, effectively ending the worst of the Covid pandemic.
Medical revolutions are like evolutionary punctuated equilibrium -- barriers to advancement are overcome nonuniformly and often incompletely, requiring a lot of continued effort even after a revolution begins. So it shouldn't be surprising that more battles are won than wars. We should celebrate whatever victories we can. Cancer promises to be a war to end all wars.
> I've been reading news lines over the past years about great advancements in many incurable and chronic diseases
There is a lot of overhype in the news. When they claim that a new 80% improvement in batteries we all know it's a joke a laugh. When there is a similar exaggeration in cancer cures we get sad.
The saddest part is that the overhype shadows all the small/local improvements. They are better explained in sibling comments. Medicine is not my area so they give better examples than what I can choose.
When I read a new about my area or something close enough, it's fun to try to guess what was the original new before it was badly rewrote by the press and how interesting it is. But when there are lives related to the new, it's not fun to read post with unrealistic promises.
The thing about batteries is that those big discoveries in the lab take a long time to reach the market. By the time they do reach the market, they're just an incremental improvement over all the other big discoveries that are already in production.
So we never seem to get a dramatic breakthrough, but what we do get is steady improvement over the course of decades. And that's why we have electric cars now with ranges over 400 miles, while back in 1996 the EV1 had 70 to 100 miles.
I think cancer treatments are pretty much the same.
Ok are you fr? The phone I'm typing this on is superior to the computer in highschool to play video games on and it's my old phone that can't hold a candle to my new phone. The batteries in both devices are both MORE THAN 80% superior to the battery in my first phone.
F*ck. Progress does exist - life has got enormously better but people reuse to see it and focus their entire lives on living the same day over and over and wonder why they are unhappy.
The problem is that most of the 80% advance in your batteries are small 2-3% advances that never got a huge press cover. The 80% improvement press announcement are the unrealistic ones.
PS: My favorite weird quantum anecdote that nobody know and everyone uses was Giant Magnetoresistance. Have you ever read about it? Do you have a device that uses it at your home? Is it weird to have two currents instead of one? https://en.wikipedia.org/wiki/Giant_magnetoresistance But now the SSD ruined the anecdote :( .
When my Aunt was diagnosed with MS in the 80s it was a crippling and degenerative ailment.
When my brother was diagnosed with MS ~30 years later, it was a nothing burger. He gets an infusion monthly and suffers no significant impact on his quality of life.
This is great to hear. I had an Aunt that was diagnosed with MS around 40 and by 50 she was in long term care - it's the only place I ever saw her and she had a terrible quality of life, completely incapacitated. I've always had a fear of MS bc of this bc apparently she was completely normal before.
> I really find strange how I've been reading news lines over the past years about great advancements in many incurable and chronic diseases (like Alzheimer's, diabetes, and cancers) yet after all that time people's treatment is not going any better.
... I mean I think you are possibly not just paying attention. All sorts of things that were absolute death sentences within recent memory are now very treatable. News articles tend to overhype, of course, but cancer treatment now is a different world to a few decades ago.
> TIL that scientists at Stanford University have developed a smart toilet that reads your anus like a fingerprint and monitors the health of your poop and pee. The lead researcher said, "We know it seems weird, but as it turns out, your anal print is unique."
I had a tech startup back in the day and I always had a hard time getting people to understand the significance of data and ended up often explaining how incredibly valuable the data is about when we simply take a sh*t is/would be. Most people couldn't seem to grasp that either.
Cancer deaths have been falling since the 90's. Detection and treatments are improving.
We don't have a silver bullet because these diseases are so incredibly complicated. "Cancer" is a particular type of disease behavior, but is essentially a broad class of failure states across different types of cells and tissues, with different genetic, metabolic, biochemical, and molecular dysfunctions.
The decline in cancer deaths can almost entirely be explained by the decline in smoking. Getting from 40% of people smoking to 15% was probably the biggest public health victory of the latter half of the 20th century
It's true that there has been some progress in treating most cancers and particular success in treating some specific cancers e.g. with checkpoint inhibitors. But lung cancer is both one of the most common forms of cancer (it's still third even with the massive decline in smoking) and has a much lower 5 year survival rate than the other most common cancers, breast and prostate. The massive decline in smoking has played an outsized impact on the improvement in reducing both cancer rates and deaths from cancer generally
This is true in the large sense but it obscures that 5 year survival rates have been steadily extending for many people who already have cancer. Treatments are in fact improving
Remember Calico and Altos Labs which were moonshot cure longevity companies? After years they emerge out of stealth and all they got is some cancer drugs. The gravitational pull of the billions of dollars to treat cancer patients and extend their lives a few more months eats up all the attention of the biotech world because there is such an astronomical amount of money in it and you'll just have to come up with a new way to kill cells which is relatively easy.
So usually when people talk about new cancer drugs it meant that great scientists will make billions wasting their lives barely improving the quality of life for some terminally ill cancer patients and it's just kind of sad, honestly.
There have been a fair number of announcements about possible progress, and even several recently related drugs. The research and drugs continue to focus entirely on beta amyloid buildup in the brain:
There's not a shortage of debate on whether they are effective, ought to have gotten any approval, or if beta amyloid buildup is even a cause or contributor to Alzheimer's disease, so whether we've actually made progress remains debatable for the short term until results on these drugs are in.
Wasn't a lot of the beta amyloid buildup hypothesis based of of results from Marc tessier Levine who left Stanford under a cloud of accusations of results fakery and is now the CEO of the ai startup xaira?
A lot of it is the case of bad science being popularized and then blindly built upon. This is exampled by the recent redaction of a huge amount of Alzheimer's papers which formed the nucleus of Alzheimer's research. Academia and science are often the largest purveyors of misinformation despite.
mrna vaccine had big “breakthroughs” during the 80s and 90s and yet it took quite a while for it to be a viable thing. some things take time and some things never pan out past the in a pitri dish stage.
This all makes sense once you consider health as a business. There is no great interest by business in a cure to this or that. However, an expensive perpetual treatment (lifetime service contract) is far more appealing - the revenue stream is superior.
What we call a 'health' industry is a misnomer - it is a sickness industry, like the ministry of defence is really the ministry of attack.
If you want to really get cynical, you can consider the possibility that a lot of treatments are not only unnecessary, but actively detrimental to the person receiving the "treatment". The person in future may develop diseases that will then open further revenue streams from what would otherwise be a healthy individual. This would assure a healthy pipeline of future revenue for the pharmaceutical companies.
Luckily we have government agencies to manage the pharmaceutical products we are given. Unfortunately, it is something of an open door policy as senior government staff are then given senior positions in pharmaceutical companies.
> There is no great interest by business in a cure to this or that
Of course there is. Cures make billions.
This might be a conspiracy theory stupider than flat Eartherism. It requires not only every Western pharmaceutical company’s collaboration, but also every one in every other country, and also all the public labs, and every world leader and their families to suck it up for the conspiracy’s sake.
Most people act against their conscience pretty much every day for money, more so in senior positions. That money is a great motivator is not really a conspiracy.
Go beyond the YouTube video reporting on the report's title and you'll find a thoughtful paper on drug pricing. TL; DR Sick people and governments will pay a lot for cures.
> Most people act against their conscience pretty much every day for money, more so in senior positions
This isn't about conscience, it's about greed. Cures are great business. Also, again, rich people get cancer. If you want to come up with healthcare conspiracies, don't pick a disease the rich and powerful get.
Trials? No. There are various other countries you can go to in order to have these unapproved treatments performed, at great personal cost because there are no economies of scale. But there largely aren't countries performing trials that would count as an FDA Phase II or Phase III trial.
You specifically mentioned the FDA as being a problem; are you suggesting that approval in general is the problem, and no approval should be required anywhere?
i find this funny. what do you mean "patient's own risk?"
that has always been the case. you go for a minor surgery, you sign a waiver. you go to a doctor, they are supposed to give reasonable care. No one can guarantee success. the same with lawyers or drivers or mechanics or technicians. basically anytime you go to someone for assistance, they can't guarantee anything. the person is themselves always responsible for everything.
Of course there’s always some risk with any drug or medical procedure. But - obviously - not all risk is equal. Unapproved treatments are riskier because they haven’t been proven effective, and they haven’t been well tested for side effects. There is an uncountably large list of cases throughout history of people willing to sell ineffective and/or actively harmful treatments, which is the whole reason the FDA exists. Look up people who died taking ivermectin for Covid [1], or just pick any ailment and do some research on fake treatments, perhaps cancer for example [2]. The UN says half a million people in Africa alone are being killed every year by fake medicine today, currently [3].
History is also full of examples of treatments that do work under unknown (at the time) circumstances and were standardized into common practice through trial and error. This includes most over the counter medication and procedures today.
Most of that advancement stopped with the introduction of the FDA and its equivalents in other countries.
The story of efficacy trials falls apart when you consider the complex reality of the human body and pharmaceutical action. There are many medical procedures and drugs which we know work on certain patients some of the time, but we are prevented from giving to new patients because the high standards of Phase III efficacy haven’t been met.
So what? The U.S. food and drug laws aren’t protecting against things that accidentally work, they are protecting against things that don’t work. These laws are hard won and represent many people lost to both ignorance and greed.
If something has efficacy, then trials will eventually prove it, it’s just a matter of time. You just made a case that the process works. If efficacy can’t be shown, then it’s very risky for people to try the treatment, riskier than using something with known outcomes, and potentially riskier than doing nothing at all.
Either way this is all irrelevant to your bogus claim at the top that the FDA has anything to do with the perception that treatments aren’t improving. The top comment’s hypothesis is incorrect, which adds to the multiple reasons your proposed explanation is wrong.
Inducing ketogenesis whose byproduct is the retention of water and generation of ATP has historically acted as an epiphenomenal method of apoptosis. Survival rates vary but fasting has proven to be an effective method.
A ketogenic diet or a strict fasting regimen are two health strategies that are too frowned upon, still, and unfortunately so. Food (or whatever passes for "food" in modern times) has become such a crutch, and people have such potent emotional ties to it, that the sole idea of restricting one's diet will come across as negative from the get go. Nonetheless, there have been advancements in that regard, culturally, I believe.
Apparently I'm an incredibly healthy individual - just had a physical that stated that. I do have a good genetic base but in general I don't live a particularly healthy lifestyle, my activity is pretty much the same as everyone else - except my diet.
I'm a vegetarian and a celiac (no gluten) so I don't eat a lot of processed food. Rice, oatmeal, corn tortillas, black beans, cheese, hemp hearts, flax seeds, chia seeds, Sriracha, coffee w/honey and hazelnut creamer - all that is easily 90%+ of my diet. I also drink a protein drink called OWYN daily.
About once a week I'll have a little to eat in the morning and then I just won't really get hungry again til really late and I'll often just not eat then and go to bed. Intermittent fasting is great. A few times a year I'll go a few days without really eating - there are so many benefits to the process. The primary being autophagy - that I sus is the reason I look so much younger than people my age.
The science of sleep radically disagrees with the next thing I'm about to say.
The process with food and the body is very similar to the process of sleep and the brain.
Occasionally pulling an all nighter playing video games (can't be a stressful all nighter) is actually good for you - it resets some stuff in your head. This can be particularly effective for dealing with certain states of depression or melancholia.
Firstly im so sorry to hear this. I can completely empathise as i lost my father who was my best friend to Pancreatic Cancer. Like you, one day we were fine and joking, the next day my world collapsed with the news. Uncontrollable sadness, then anger, then desperation and the why me / why my dad. I just wanted to write to you to say that you are not alone. You dont know me, i dont know you, but i wish you and your partner well and send thoughts and love. It is a surreal thing to happen. I remember looking at other people living their regular lives smiling and laughing and thinking, how can they be happy. An unbelievable amount of varied emotions. Seeing really unhealthy people, or bad people on the news, and i know this sounds bad, but wondering, why us, why not them. Just mind spinning type stuff, a plethora of every conceivable emotion. I hope you have loved ones you can vent and talk to. Again, you’re not alone.
Thank you. I can relate to everything you're saying.
I think what's been helping has been reading about death and what that means and potentially feels like. I think part of the issue is that the topic of death is so misunderstood and feared, that it creates no reasonable way forward mentally. So hopefully I can learn more about that over the coming weeks.
It's been a very weird 6 weeks. It's like, everything was fine. We had our normal suburban life. Things were going great. We had just celebrated our daughter's first birthday.
Then it's like, you realise that everything you had imagined over the next 40 - 50 years is suddenly not going to happen anymore, and it just feels so surreal.
Thankfully, a lot of the initial hysteria is gone. But there's definitely a sense of "why me?"
Sorry about your partners disease. Learning such news about loved ones is difficult.
I have a chronic condition and spent years wondering "why me?". Now my thoughts are more like "why not me?" and to try and embrace what life we're lucky to get and live day by day. Godspeed
Regardless of your religious background, the Book of Job is deep, and sort of boils down to “Why not you? There’s much you don’t understand”.
I myself became Eastern Orthodox about 15 years ago, which has a somewhat different view of death than Western European Christianity (1). There’s also an acceptance that death occurs and that we prepare for it in our hearts, while still believing that death isn’t “natural” state. It’s a dichotomy of beliefs, but helped me accept both the reality of death but a hope for more. I pray and also love the funeral prayer in Orthodox Churches of “may their memory be eternal”. Very beautiful.
I also find the Stoic philosophers (Marcus Arelius, Epictetus) to hold to an acceptance of death and similar views of preparing oneself for it as Orthodox do. They discuss the concept of “memento mori” (2) which plays a big role in Stoic Philosophy. They focus on directing one’s internal emotions to gratitude of time with loved ones and settling anything weighing on your heart, if I understand them.
At the end of the day, both focus on preparing ourselves to realize we can die any moment and really don’t have any “right” to life. That it’s better to view each day as such and to find gratitude and peace with loved ones while you can instead of focusing on ourselves and expectations of life. We can and should feel sad and disappointed but also to not become lost in it.
Apologies for the poor writing. I’m writing on my phone and well it’s a hard topic. My mother passed away last year way too young and there’s always a feeling of loss.
Time slows down. We spent our lives week by week. I was her care taker and hope-keeper, and I would share oncology news like this with her to help keep our family sane. I think it helped.
The "why me" for others is the first time they realize they have a chronic illness, that sudden realization that the universe is an uncaring dance of atoms, the realization that every attempt at ordering it's just a house of cards, including our DNA and everything else we rely on. I was expecting myself to land that line of reasoning into some comforting words but I have failed miserably ha, hold on tight.
“There is no justice in the laws of nature, no term for fairness in the equations of motion. The Universe is neither evil, nor good, it simply does not care. The stars don't care, or the Sun, or the sky.
But they don't have to! WE care! There IS light in the world, and it is US!”
― Eliezer Yudkowsky, Harry Potter and the Methods of Rationality
I don't like this quote because it suggests a sort of separation between ourselves and the universe, or it suggests that the universe is some all-powerful omnipotence that might deign to heal us if only we could supplicate ourselves to it, but that's mistaken.
We're made of all the same stuff as those stars. We are the universe, and if we care, that means the universe cares as well. When we have the power to do something, that means the universe has the power to do something.
Mattigames, there is a logic flaw in your little aphorism that seems quite telling. Since you and I are part of the Universe, then we would also be indifferent and uncaring. Perhaps you forgot, mattigames, that we are not superior to the Universe but merely a fraction of it.
Hard to tell. The cynical response is that the novelty is that it's coming from Stanford. The perhaps more correct response is that the novelty is the mechanism of triggering the apoptosis and the specificity.
Here's a paper from 2018 that discusses the prospect of using apoptosis for cancer treatment. They even talk about BCL-2.
Triggering the automatic cell death on demand, instead of a period of time, i.e. apoptosis, sounds pretty smart and novel.
After 7 years all of our cells die and regenerate, but using biochemistry and some endogenous proteins glued together to control that period of time, i haven't heard about it before.
Not a medical expert, but cancers have a vast number of variations in the type of the cancer cell they create, but one common characteristic of all cancers is that they are derived from our own cells. So they should respond to some "commands" our own cells follow.
Inducing apoptosis for cancer prevention and treatment is old news though. Fasting, water fasting that is, causes apoptosis of cells en mass and has proven to be very effective in minimizing radiotherapy or chemotherapy sessions, and even a total treatment. Instead of doing 20 chemotherapy sessions, reducing it down to 1 or 2 and the cancer is gone.
Anyway, someone doing the same using a biochemical pathway and light up gene expression, is pretty novel.
I think you’re overstating the “proven” effect of water fasting. That said I’m surprised and happy to see that several academic medical centers are running trials of fastingin conjunction with chemotherapy.
I meant "proven" when done by the patients themselves, not by the doctors necessarily.
Dr. Gundry has done an interview with a martial arts guy who was diagnosed with cancer, and fasted for 20 days only water, and 20 days a little meat and nothing else, and one or two sessions of chemotherapy or radiotherapy later he was clear of cancer. There are many people who talk about same experiences, from the patient side.
If some doctors are seriously researching fasting and cancer treatment, that's going to produce some measurements instead of relying on anecdotes.
I cannot find Gundry's interview, it's 5 years old something like that.
You’ll find anecdotal “evidence” for all sorts of stuff when it comes to cancer. Some of it is just woo, others might just work for really specific genetic mutations, etc.
Fasting in general has been known for quite a while but (and I’m far from an expert) it only helps with certain cancers. Hell, I had a friend die this year from stomach cancer and he literally couldn’t eat or drink. He only went to the hospital when he was already skin and bones, got a few chemo treatments, and then it was too late.
Is this still working? Am I being blocked at the ISP level?
For me sci-hub.pub opens a simple page listing other sci-hub URLs, but each and every one of them fails, ending in "Unable to connect" as if the server did not exist. (Tested: sci-hub.ee, sci-hub.ren, sci-hub.ru, sci-hub.se, sci-hub.st, sci-hub.wf).
Is sci-hub still working for people, I haven't been able to use it for a while.
edit: Wow, it works if I go there via VPN… incredible. So sci-hub is illegal in France?
This seems too straightforward to be credible? If I was researching in this field surely this is the first thing I’d try?
If it is indeed credible … this sounds like the “CRISPR moment” of cancer treatment, sure. And I’m really happy for that.
But I will be honest and write what I’m thinking: if this is real then frankly I’m disappointed it took this long. Do we really have our best people working on cancer? I have known so many who died waiting.
It seems like there has been roughly the same investment this decade (around $200B) in climate tech compared with cancer research, and yet electric cars and batteries are now a “solved problem” that’s just waiting to scale. The progress with Cancer is noticeably less. Is the money being well spent? Or are we donating $100B-s for researchers and labs to sit on a gravy train making sub tier progress.
Here’s a wild theory. Perhaps as a society we built the wrong prerequisites to get into cancer research and we filtered out all the Mozart’s and Leonardo’s…
It took time to know what each protein does in a cell (we still dont really understand most of them), it took time to find all the ways that various cancers use the protein machinery in the cell to their benefit (new ways are still being discovered these days), it took time to think about molecular glues and turn them practical, and it took time to build the right chemistry and then test it (it takes time even after you know all of the previous steps.) It will still take years, possibly over a decade before this particular development can lead to a drug that passes human clinical trials and is eventually approved. It is not the lack of geniuses that slows things down, rather it is the very careful consideration of risks to minimize the loss of human life during experimentation, and the attempt to optimally allocate the resources across too many different challenging problems in order to maximize the long term benefit to society. The true amount of money spent in cancer research is much higher than the $200B over a decade that you mentioned, however the vast majority of it is just capital losses of various companies spent on the tools and research in early stage discovery across tens of thousands of projects, and a separate huge and more obvious chunk goes to attempts and failures at human clinical trials. The cost of drug discovery has stopped increasing exponentially during the last decade but is still pegged at several billion dollars per approved drug without counting costs from competitors who never get anything approved.
> If I was researching in this field surely this is the first thing I’d try?
Let me ask a clarifying question: Are you saying that the first thing you would have tried is to synthesize bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs)?
Or are you just saying that you would have tried to drive cancer cells to self-destruct (but have no clue how)?
> With a little domain knowledge and research you find out pretty quickly
That's cool. Where do you think that domain knowledge comes from? Did we just found it in a fortune cookie? Or does the cancer research conducted has something to do with that we have this knowledge?
> BCL6 is lymphoma.
That's not correct. BCL6 is a protein, or a gene which codes that protein. Mutations in BCL6 can lead to B cell lymphomas. BCL6 is not lymphoma.
> I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present.
Excellent. Sounds like you are an oracle of oncological research roadmap. What should be the next target to develop drugs for?
I am glad that you know these things, but cancer research has still failed society as a whole.
3 of my immediate family have had cancer, 2 took chemo and it ruined their lives (it caused weak bones, their spines to virtually dissolve, which led to surgeries to insert plates and things, which have failed multiple times, it has been a mess).
The third was not eligible for chemo because they were too sick and they had an existing case of lupus. So we started trying things -- probably 100 different things at first. What worked for them is taking Sanguinaria canadensis daily orally. It is now 15 years later and they still have cancer but are living a normal and healthy life.
You know, despite being the most effective treatment you could possibly hope for in this situation (besides an actual cure), there are only a few papers on Sanguinaria canadensis, and most research discredits it. Other friends of mine have tried chemo and died in a horrible way. Now you understand my criticism of cancer research. For all the money that has been spent, the most viable treatment available through a hospital is still a living nightmare.
I am tired of news like this that never gets anywhere. We have a billion way to destroy cells, great. Let's get a reliable delivery system working now. While that is in the works, I will stick to fasting and other simple methods of decreasing oxidative load.
As someone who tried to keep a cancer patient alive for as long as possible, this type of news offers hope, and encourages young people to become oncologists and researchers, which we so desperately need.
The entire point of this research is to develop a targeted delivery mechanism based on malfunctioning gene activations. It's a simple but clever approach IMHO.
No, this whole spiel of big pharma wanting to keep people sick is insane. That could work if there was a single pharma company in the world, but all it takes is one company making an effective cure for a disease and they will make big bucks. Even if you think the people in charge are evil profiteers, we all win in the end
There's a decent amount of cynicism in the comments, which I understand. I think this is a really cool and novel study, though.
Historically, cancer was treated with therapies that are toxic to all cells, relying on the fact that cancer cells divide quickly and are unable to handle stress as well as normal cells (chemotherapy, radiation).
The last couple of decades we've seen many targeted cancer therapies. These drugs generally inhibit the activity of a specific protein that lets the cancer cells grow (e.g. EGFR inhibitors) or prevents the immune system from killing the cancer cells (e.g. PDL1 inhibitors).
This mechanism is way more interesting. The gene BCL6 is usually turned on in immune cells when they are mutating to recognize foreign invaders. This process involves lots of DNA damage and stress, but BCL6 stops the cells from dying and is therefore important for normal immune function. Unfortunately, this makes BCL6 a gene that is often co-opted in cancer cells to help them survive.
The method cleverly exploits the oncogenic function of BCL6 not by inhibiting it, but by turning it into a guide, enabling the delivery of activating machinery to the targets of BCL6 and reversing the inhibitory effects on cell death.
The whole field of targeted degraders, molecular glues, and heterobifunctional molecules is a growing area of interest in cancer research.
This comment hits the nail on the head. Another big consideration with the technology in this paper that hasn't been mentioned in this thread is that it opens up a huge range of possibilities for targeting "undruggable" protein targets. Most drugs are small molecules that bind to sites an (relatively much larger) proteins, thereby getting in the way of their function. Unfortunately the vast majority of proteins do not have a site that can be bound by a molecule in a way that 1) has high affinity, 2) has high specificity (doesn't bind to other proteins) and 3) actually abolishes the protein's activity.
With "induced proximity" approaches like the one in this study, all you need is a molecule that binds the target protein somewhere. This idea has been validated extensively in the field of "targeted protein degradation", where a target protein and an E3 ubiquitin ligase, a protein that recruits the cell's native proteolysis machinery, are recruited to each other. The target protein doesn't have to be inactivated by the therapeutic molecule because the proteolysis machinery destroys it, so requirement #3 from above is effectively removed.
The molecule in this study does something similar to targeted protein degradation, but this time using a protein that effects gene expression instead of one that recruits proteolysis machinery. The article focuses on the fact that cancers are addicted to BCL6. This is an important innovation in the study and an active area of research (another example at [1]), but leaves out the fact that these induced proximity platforms are much more generalizable than traditional small molecules because it's the proteins that they recruit that do all the work rather than the molecules themselves. This study goes a long way to validate this principle, pioneered by targeted protein degradation and PROTACs, and shows that it can be applied broadly.
[1] https://www.biorxiv.org/content/10.1101/2024.07.27.605429v1
I haven’t read the paper yet but the news article seemed a bit, meeh.
BCL-2 inhibitors, mainly Venetoclax, is used in cancer therapies quite often which also triggers cell apoptosis and it’s very effective. It was also designed to target B-cell related cancers, but it found to be so effective that FDA approved it to be used in primary cases of Acute Myeloid Leukemia. So, killing cancer with triggerring apoptosis is very well known. I think the novel part might be the two protein, so it is probably more targeted for metabolic activities… but yeah didn’t read the paper yet.
Anyways, for the side effects a major one could be Tumor Lysis Syndrome (TLS). Basically, if you apoptose the cancer cells super fast, the molecules from those cells spread everywhere and it becomes toxic for the patient. This is at least the case for Venetoclax.
How much cancerous cells are similar to let us know how to target them and deliver a payload?
I guess some payload delivering mechanisms expect very 'standard' features from cancer cells?
Cancerous cells are fairly diverse across individuals, or even within a single individual, and many biological treatments require precise sequencing of the tumor DNA of that individual patient to adjust and work. In some cancers, there is a nasty "Russian roulette" effect in play, where a certain treatment may be extremely efficient (in practice a cure, even though oncologists avoid that word) in people with a certain mutation and totally useless in others, even though from the macroscopic point of view, their tumors look the same.
Then, basically, each cancer, cancer cells should be sequenced, then based on the type of cell and DNA sequencing, we have a list of "tools" to deliver payload to those very cells (without delivering such payload to sane cells, ofc)?
That would be the ideal scenario, yes.
In practice, we can only make use of some known mutations. Not just for delivering chemicals, but also for "teaching" the immune system to attack such cells, which, once it is able to recognize them, it will do vigorously.
Let's hope that this catalogue will grow until it covers at least all the typical cases.
What would be the kinds of expected side effects of such approaches?
My understanding is that even though immunotherapy's mechanism may seem more natural than chemotherapy and radiation, and in some instances may be a magic bullet, up-regulating the immune system can have serious consequences. I remember reading about a clinical trial showing similar progression free survival but increased grade 4-5 toxicities (requiring hospitalization or being fatal). My assumption was that these are autoimmune conditions that are aggravated in some of the patient population.
oop talked about mechanism, so we can't know side effects here. someone will publish a new drug that relies on this mechanism, and then they will check the side effects of the specific drug on cells, rats, or other experimental species.
All of this stuff is promising, and I hope the diagnostic side catches up as well.
Just went to a funeral this weekend for a 40 year old who died of breast cancer 4 weeks after diagnosis at her first annual mammogram.
A lot of skeptical people under 30 here haven't lived through regularly various cancer diagnoses in their friends & family group that your late 30s/early 40s starts to bring.
I don't have the data on it, but anecdotally I notice that women's cancers seem to strike 5-10 years earlier than mens even if they can be caught early & treated well.. Though apparently men have overall worse cancer survival rates.
I'm finishing my PhD in hyperpolarization (hopefully) soon. In my opinion, hyperpolarization will significantly contribute to early-stage diagnosis. We're designing machines, processes, and chemicals that create novel contrast agents for MRI, enabling the localization of cancer cells and even tracking their metabolism. For example, it's possible to inject hyperpolarized pyruvate and track its conversion to lactate. Essentially, this technique boosts the MRI/NMR signal of the contrast agent by up to 100,000-fold. When the contrast agent undergoes metabolism, it creates a unique signal footprint through chemical shift changes, which can aid in characterizing cancer.
I have a question, if you don't mind. What are the nuclei polarized relative to? The molecules in a liquite rotate a lot and I am curious whether the nuclear spins stay aligned with the electron systems or if they remain fixed in an inertial frame.
There are two semi-connected concepts at play here. Polarization in this context refers to the ratio of neutralizing (i.e. "up" vs "down") spins in a given system. For most nuclei in organic systems like protons, carbons, and nitrogens, this ratio is naturally very small, which is the reason that magnetic resonance approaches like MRI usually have poor signal-to-noise. Hyperpolarization techniques usually involve the transfer of polarization from a source of high ratio, like a free electron, to a relevant target (in the original poster's example, 13C in pyruvate). The polarization in this case is hyperpolarized 13C, which has an "up"-to-"down" spin ratio that is much higher than regular 13C, which makes the signal-to-noise that you get from the pyruvate much higher than it would be otherwise. Tumors love pyruvate so this approach means that tumors will light up like a beacon in your MRI.
The physical rotation/tumbling of molecules in an MRI is also very important, because the strong magnetic field is the thing inducing the "up"-vs-"down" split in the first place, and if the molecular motion is happening at a certain frequency with respect to the external magnetic field there are other interactions that can come into play which can affect the coherence of the nuclear spins (i.e. they can fall out of sync). Thankfully, the rotation of a small molecule like pyruvate is very fast (might higher then the "spin" frequency-a.k.a the Larmor frequenct of 13C at the magnetic field strengths involved in MRI) so the physical tumbling of pyruvate doesn't really come into play when trying to measure its signal. It can be another story for molecules that don't tumble quickly, like the ones that make up tissues, fat, etc.
Great explanation. Indeed, the "rotation/tumbling" is nothing to worry about. One of our biggest challenges is relaxation. The moment we polarize, the clock ticks. Usually, the time scope is around 15-90s. I'm in the field of para-hydrogen and built automated systems which carry out the chemical reactions, polarization transfers and sample cleaning. Many hyperpolarization experiments with para-hydrogen prefer nasty solvents as chloroform or methanol. It is a technical challenge to replace them by water within seconds. One of my favorite topics is Xenon hyperpolarization. It's very elegant, no cleaning required, no wet chemistry, and provides amazing lung scans.
Sounds exciting. Routine periodic medical imaging seems like one of those Star Trek technologies thats in reach but not quite been implemented outside of rich countries in Asia.
Hyperpolarization also allows for cheaper MRI scanners. With hyperpolarization, you achieve polarization (needed for SNR) without the need of big magnets (=expensive). Even in rich countries, MRI scanners reach their physical and technical limits. 3T magnets are already 7-figures and costs of bigger magnets will increase non-linearly. Moreover, with higher fields, side effects increase, too.
Four weeks... I didn't know that it could be so fast. That's awful.
We were surprised, but it happens. Breast cancer can be very fast moving. Unless they have family history, women aren't told to do annual exams until you hit 40. The symptoms may not be too specific or startling even when it is into stages 3 & 4.
Worth reminding the women in your lives to check their family history and consider getting early exams either way. A lot of times it turns out women do have family history that went undiscussed until they ask mom, aunts, grandmothers, etc.
The other cancers that worry me are the slow moving imperceptible symptomless ones like pancreatic, liver, kidney, etc. Know a few people who around 50 discovered they had stage 2-3 cases due to unrelated scans they got from an accident injury. Some of these you have 5-10+ years window to treat it and live without impact to lifespan.. but most people don't catch it until stage 4 when they actually feel sick and it is too late.
Some people die by cancer, other overcome the cancer, and a small amount don't stand the treatment and die by the chemotherapy. Sometimes by genetics, and can't always be known before. It also depends on how much advanced and aggressive is the tumor.
Pancreatic cancer is the worst. Many people don't get a month.
I believe I read, but can't find the source now, that the sex-specific survival rate is mostly explained by men not catching it and starting treatment as early as women.
Even for cancers that shouldn't be sex-specific, like lung cancer, men are less likely to survive it.
This is very believable given gender differences in being on top of healthcare..
The urgent need for advancements not only in treatment but also in diagnostics
Same as mountainriver's comment. I really find strange how I've been reading news lines over the past years about great advancements in many incurable and chronic diseases (like Alzheimer's, diabetes, and cancers) yet after all that time people's treatment is not going any better. I'm not sure whether scientific journalism somehow delivered some unintended messages to me, or we're just supposed to experience these great advancements after couple of decades from the announcement.
HIV has gone from death sentence to completely preventable with a single daily pill or every 6 months injection, and readily treatable to the point where we have geriatric HIV patients. Obesity is now effectively treatable even taking into account compliance. Hep C can be cured entirely with just six months of oral medication rather than a barely tolerable intravenous course that didn't work all that well. These are massive improvements that have changed how hundreds of millions of people are treated and their prognosis.
The road to the clinic is long, but there have been very big improvements.
And stage 4 melanoma used to mean you'd be dead in a year. I know someone who got diagnosed with it almost a decade ago, got three doses of immunotherapy, and is now cancer-free. Doesn't even have to get scans anymore.
Melanoma is the main cancer that responds well to immunotherapy, PD-1 inhibitors. Other solid cancers, not so much, although in combination with other therapies, is seeing some okay results.
They recently found some types of rectal cancer to be PD-1 sensitive.
https://www.nejm.org/doi/full/10.1056/NEJMoa2201445
It seems like stock markets, a lot of bubbles pop, and it's easy to miss the trend .. every 5 years some progress is made.
Two things. If you follow the news closely, but lack specific expertise or knowledge, you develop this nihilistic sense of doom to some degree. The narrative of our age is that everything is in decline. It pulls clicks.
The other thing is that cancers are not created equal, not all treatments are evolving quickly. Your loved one may be suffering, and that’s your world.
I will say that I lost my beautiful wife a little over a year ago. She had an aggressive cancer, for which the 10-year survival rate was zero. Thanks to the miracle of immunotherapy, the five year survival rate is about 65%. At the same time, my 78 year old aunt successfully fought lung cancer that was a death sentence 20 years ago.
I’ve nothing to add to the discussion but just wanted to say that, for what it’s worth, I’m terribly sorry for your loss.
Thank you both!
I think it’s important to share for a variety of reasons but most importantly to add some humanity to a topic that gets turned into technocrat babble.
Very much the same from me. I know +1 posts aren’t generally welcome here but I hope dang can forgive it.
I’m not sure I agree. We now have techniques like immunotherapy for some cancers. Cancer rates still continue to fall.
We have a drug now that you can take so you won’t catch HIV, as well as another drug for HIV+ that keeps it at bay.
We haven’t found a cure-all. Rather, now we have a lot more treatment options nowadays depending on your specific cancer or illness.
Cancer mRNA vaccines for solid tumors are administered to real patients in clinical trials right now.
So you'd rather she them before you get cancer?
As far as I understand it these immunotherapies are tailor-made to the very specific cancer and its genetics that a patient has, which is also why the stuff is so darn expensive. So you can't have a vaccine until you already have the cancer.
And as always, when problems get solved, other problems get revealed. We didn't even really know about cancer until life expectancies got to the point where dying in your 30s is a tragedy instead of being fairly normal.
I don’t think dying in your 30s has been normal in the Western world anytime In the last 500 years. Remember all those life expectancy mean statistics were heavily dragged down by the huge infant mortality stats.
If your comment was more talking about the Stone Age or something, I apologize for misinterpreting :)
Infant and mother mortality stats.
The idea that most people more than ~120 years ago died in their 30s or 40s is a popular misconception. LEAB (Life expectancy at birth) used to be in the mid-30s, but this was largely due to a bimodal distribution of deaths: a large number dying during childbirth, infancy, or early childhood, and a lot at more typical old age (60-70, still a bit lower than is common in much of the west today, but you get the idea). If you made it past puberty, there were pretty good odds of you making it to old age.
100%. I carried this misconception after high school and college and was surprised to learn it’s completely wrong. There’s a name for the old-age end of the bimodal distribution: longevity. Longevity is the natural lifespan of people who don’t die of any early mortality factors. Most people who have the misconception are accidentally conflating life expectancy with longevity. A few unscrupulous peddlers of false hope, like Ray Kurzweil for example, intentionally conflate life expectancy with longevity to reinforce the misconception. As I was learning about longevity I started talking to my anthropologist brother about it, and he was like, oh yeah, people who don’t die from war or disease or infection have always lived to be about 80 years old for all of known history. He mentioned there’s plenty of written evidence from, e.g. Socrates’ day, and also lots of human remains that support it from ten thousand years ago.
Well we have a lot less disease and infection now!
This is why life expectancy has gone up, while longevity has mostly remained unchanged (for at least thousands of years). Longevity represents the best we can do, and life expectancy can’t exceed longevity. Life expectancy will asymptotically approach longevity as medicine improves.
I think it's worth noting that we (in the west) have a lot less of most diseases and infections now, stuff like polio, plague, malaria.
I don't suffer from delusions that we have accurate data on conditions like obesity and T2D going back to the middle ages, but we have seen incidence rates of these kinds of disease explode upwards over the last century.
I'd be interested in more detailed data broken down by disease over time.
Aside from infant morality, don't forget the massive death load from things like accidental death, famine, and maternal mortality.
E.g. from Wikipedia, female life expectancy from age 15 in Britain in the 1400-1500s century was 33 years (so reaching 48 years of age).
...and also bubonic plague.
Cancer was first documented around 3000 BC, and has been studied for a long time. https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr...
> people's treatment is not going any better
That's not true. It's improving steadily: https://progressreport.cancer.gov/after/survival , and with the newer advances it's going to become even better.
Yes, it's not like an exponential Moore's law graph, but there is a steady drumbeat of incremental steps. And they keep reinforcing each other.
Only for specific sites of cancer. Many others are just as deadly as they have ever been.
Well, yes, but that's typically how progress works in any field.
10ish years ago Myleoma was a semi death sentence, it’s now coming close to being treated like a chronic condition. There are definitely improvements happening, but we’ll often miss them because it’s incremental rather than “we developed this cure for lung cancer and it’s no longer a problem”
Edit: some of the replies below are pretty bleak “it’s just a few months that’s nothing”. The difference between a 5 year and 15 year life expectancy for a parent being diagnosed with blood cancer around 60 is huge.
I am curious: why would it make a difference for a 60 year old if they are a parent and have 5 or 15 years vs not? I would have thought by that age children are long independent...
60+15 => 75, a pretty normal "lived a full life" age.
60+5 => 65, maybe dying before you even retire from your job.
Seems significant.
The difference between your grandkids meeting you or not.
Exactly - in my father's case would be difference between dying before all your kids marry vs meeting all your grandkids, helping to watch them.. and seeing them grow up and start going to school.
Plenty of people have kids in their 40s and 50s.
Why do you think “people’s treatment is not going any better”? As far as I know, cancer outcomes have greatly improved.
It's the articles that decry "Big discovery in X".
This could be because the researchers need funding so they will hype the results as much as possible.
Then the articles need as much readership so the journalists hype the results as much as possible.
Then the people suffering from the disease want as much help as possible so they push the articles/papers to the doctors.
On the other hand, it's been my experience that GLP-1 agonsists weren't overhyped, I was completely surprised when my doctor prescribed Mounjaro for weight loss. Even after decades of articles about "NEW WEIGHT LOSS TREATMENT!" (See also phen-phen)
It's mostly the PR department of universities that boast about those big discoveries. Researchers themselves usually try to add some nuance to it.
Depends. Early cancer? Yes, outlook is getting better. Metastatic cancer? It's still very bad outcomes. (Personal experience.)
> cancer outcomes have greatly improved.
If you stop believing the bullshit headlines you will see that newer treatments simply increase OS by a few months and that's sufficient to claim significant improvement. In terms of patient outcomes, not a major difference, the cancer still kills you in the end. it's just KPI hacking.
What else is there? Are you saying immortality or bust?
What else is there? Long term remission for example. This is hardly looked at because we don't see any difference.
Long term remission is just a few months extra to live. In the end you have people who die quickly and people that live for years. That's why you get averages of a few months extra.
Cancer detection/testing has gotten a lot more attention. Detected early, many victims are still alive after 5 years and considered "cured." But it still gets you in the end. A lot of expense and misery while under medication/chemo/rad/surgical therapy and in the end you are dead just the same.
That’s the measurement that a lot of Covid deniers liked to roll out. Death isn’t the only metric.
Life is a precious and personal thing. Those years mean wishes fulfilled, graduations and weddings celebrated, life lived.
I'm not sure why this matters. In the end we're all going to die, death is inescapable. The ultimate form of your rationalization is that we should simply not treat anything because we die all the same.
But for many cancers and other diseases not only has early detection gotten better but so has treatment and prognosis. Treatment isn't nearly as bad to go through and long term survival rates are higher. People can live longer with cancer while still being fully functioning.
Each medical innovation overcomes but one hurdle on a path to a treatment/cure, often revealing new hurdles that weren't visible (or important) until the first hurdle fell.
A good example is lipid nanoparticles, which for the first 15 years or more of their existence were horrifically lethal in every hominid, making their potential for delivering transformative genetic or immune cargo into cells impossible. Finally, PEGylation was introduced into their formulation, bypassing the toxic effect they had in precipitating out nearly all of each animal's platelets upon treatment. Within just a few years, LNPs became a very effective way to deliver MRNA vaccines to BILLIONS of human patients, effectively ending the worst of the Covid pandemic.
Medical revolutions are like evolutionary punctuated equilibrium -- barriers to advancement are overcome nonuniformly and often incompletely, requiring a lot of continued effort even after a revolution begins. So it shouldn't be surprising that more battles are won than wars. We should celebrate whatever victories we can. Cancer promises to be a war to end all wars.
> I've been reading news lines over the past years about great advancements in many incurable and chronic diseases
There is a lot of overhype in the news. When they claim that a new 80% improvement in batteries we all know it's a joke a laugh. When there is a similar exaggeration in cancer cures we get sad.
The saddest part is that the overhype shadows all the small/local improvements. They are better explained in sibling comments. Medicine is not my area so they give better examples than what I can choose.
When I read a new about my area or something close enough, it's fun to try to guess what was the original new before it was badly rewrote by the press and how interesting it is. But when there are lives related to the new, it's not fun to read post with unrealistic promises.
The thing about batteries is that those big discoveries in the lab take a long time to reach the market. By the time they do reach the market, they're just an incremental improvement over all the other big discoveries that are already in production.
So we never seem to get a dramatic breakthrough, but what we do get is steady improvement over the course of decades. And that's why we have electric cars now with ranges over 400 miles, while back in 1996 the EV1 had 70 to 100 miles.
I think cancer treatments are pretty much the same.
Ok are you fr? The phone I'm typing this on is superior to the computer in highschool to play video games on and it's my old phone that can't hold a candle to my new phone. The batteries in both devices are both MORE THAN 80% superior to the battery in my first phone.
F*ck. Progress does exist - life has got enormously better but people reuse to see it and focus their entire lives on living the same day over and over and wonder why they are unhappy.
Mmm... I think we?
The problem is that most of the 80% advance in your batteries are small 2-3% advances that never got a huge press cover. The 80% improvement press announcement are the unrealistic ones.
PS: My favorite weird quantum anecdote that nobody know and everyone uses was Giant Magnetoresistance. Have you ever read about it? Do you have a device that uses it at your home? Is it weird to have two currents instead of one? https://en.wikipedia.org/wiki/Giant_magnetoresistance But now the SSD ruined the anecdote :( .
> yet after all that time people's treatment is not going any better.
What is your basis for this claim?
When my Aunt was diagnosed with MS in the 80s it was a crippling and degenerative ailment.
When my brother was diagnosed with MS ~30 years later, it was a nothing burger. He gets an infusion monthly and suffers no significant impact on his quality of life.
This is great to hear. I had an Aunt that was diagnosed with MS around 40 and by 50 she was in long term care - it's the only place I ever saw her and she had a terrible quality of life, completely incapacitated. I've always had a fear of MS bc of this bc apparently she was completely normal before.
Thank you for that comment.
> I really find strange how I've been reading news lines over the past years about great advancements in many incurable and chronic diseases (like Alzheimer's, diabetes, and cancers) yet after all that time people's treatment is not going any better.
... I mean I think you are possibly not just paying attention. All sorts of things that were absolute death sentences within recent memory are now very treatable. News articles tend to overhype, of course, but cancer treatment now is a different world to a few decades ago.
Robust biomarker monitoring in toilets would lead to a 95% reduction in cancer deaths.
Robust biomarker discovery in toilets would let us take care of most of the other 5%.
That's the main obvious humanitarian purpose of our project www.molecularReality.com
How do I buy an anticancer toilet?
Post I spotted earlier today on reddit:
> TIL that scientists at Stanford University have developed a smart toilet that reads your anus like a fingerprint and monitors the health of your poop and pee. The lead researcher said, "We know it seems weird, but as it turns out, your anal print is unique."
https://old.reddit.com/over18?dest=https%3A%2F%2Fold.reddit....
I had a tech startup back in the day and I always had a hard time getting people to understand the significance of data and ended up often explaining how incredibly valuable the data is about when we simply take a sh*t is/would be. Most people couldn't seem to grasp that either.
Cancer deaths have been falling since the 90's. Detection and treatments are improving.
We don't have a silver bullet because these diseases are so incredibly complicated. "Cancer" is a particular type of disease behavior, but is essentially a broad class of failure states across different types of cells and tissues, with different genetic, metabolic, biochemical, and molecular dysfunctions.
The decline in cancer deaths can almost entirely be explained by the decline in smoking. Getting from 40% of people smoking to 15% was probably the biggest public health victory of the latter half of the 20th century
That's not true. Survival rates in most cancers went up, not only in lung cancers.
It's true that there has been some progress in treating most cancers and particular success in treating some specific cancers e.g. with checkpoint inhibitors. But lung cancer is both one of the most common forms of cancer (it's still third even with the massive decline in smoking) and has a much lower 5 year survival rate than the other most common cancers, breast and prostate. The massive decline in smoking has played an outsized impact on the improvement in reducing both cancer rates and deaths from cancer generally
This is true in the large sense but it obscures that 5 year survival rates have been steadily extending for many people who already have cancer. Treatments are in fact improving
similar arguments have been made about lead and leaded gasoline being made illegal in the 70s.
Remember Calico and Altos Labs which were moonshot cure longevity companies? After years they emerge out of stealth and all they got is some cancer drugs. The gravitational pull of the billions of dollars to treat cancer patients and extend their lives a few more months eats up all the attention of the biotech world because there is such an astronomical amount of money in it and you'll just have to come up with a new way to kill cells which is relatively easy.
So usually when people talk about new cancer drugs it meant that great scientists will make billions wasting their lives barely improving the quality of life for some terminally ill cancer patients and it's just kind of sad, honestly.
Or maybe heroic efforts are being made to solve a very hard but worthwhile problem?
You don’t get to decide how long the road is to a complete solution. Just whether it will be worth it incrementally and in the end.
You don’t propose any constructive alternative.
Life, even just extending life of millions of people a bit, survival rates just a bit, is worth a lot.
Here's your alternative that precisely nobody is going to make any money off of : https://isom.ca/article/targeting-the-mitochondrial-stem-cel...
I don’t think we’ve made any progress in Alzheimer’s. Where did you read that we have?
There have been a fair number of announcements about possible progress, and even several recently related drugs. The research and drugs continue to focus entirely on beta amyloid buildup in the brain:
https://www.science.org/content/article/new-alzheimer-s-drug...
There's not a shortage of debate on whether they are effective, ought to have gotten any approval, or if beta amyloid buildup is even a cause or contributor to Alzheimer's disease, so whether we've actually made progress remains debatable for the short term until results on these drugs are in.
Wasn't a lot of the beta amyloid buildup hypothesis based of of results from Marc tessier Levine who left Stanford under a cloud of accusations of results fakery and is now the CEO of the ai startup xaira?
Yes it was mostly a bad hypothesis on which the industry wasted billions and 20 years.
Well, which is it “great advancements“ or “possible progress “?
You’re both saying two different things.
Well, let's see.
Some drug company or group of investors must think it's potentially profitable to develop into a real treatment.
Then they have to move up the trials ladder, from mice to humans and the steps in-between.
Then they have to get regulatory approval.
Finally, assuming the steps prior didn't fail horribly, they need to set up the manufacturing for the drug.
All the meanwhile handing off money to a bunch of people who, more likely than not, never worked for the company in the form of earnings-per-share.
So, yeah, a couple decades.
A lot of it is the case of bad science being popularized and then blindly built upon. This is exampled by the recent redaction of a huge amount of Alzheimer's papers which formed the nucleus of Alzheimer's research. Academia and science are often the largest purveyors of misinformation despite.
> great advancements in many incurable and chronic diseases (like Alzheimer'
There is virtually no new treatment for Alzheimer for 20 years and no progress in understanding its mechanism either.
Yep, breakthroughs get announced, but the real-world impact can feel slow
The missing ingredient that makes it make sense is the profit motive.
mrna vaccine had big “breakthroughs” during the 80s and 90s and yet it took quite a while for it to be a viable thing. some things take time and some things never pan out past the in a pitri dish stage.
This all makes sense once you consider health as a business. There is no great interest by business in a cure to this or that. However, an expensive perpetual treatment (lifetime service contract) is far more appealing - the revenue stream is superior.
What we call a 'health' industry is a misnomer - it is a sickness industry, like the ministry of defence is really the ministry of attack.
If you want to really get cynical, you can consider the possibility that a lot of treatments are not only unnecessary, but actively detrimental to the person receiving the "treatment". The person in future may develop diseases that will then open further revenue streams from what would otherwise be a healthy individual. This would assure a healthy pipeline of future revenue for the pharmaceutical companies.
Luckily we have government agencies to manage the pharmaceutical products we are given. Unfortunately, it is something of an open door policy as senior government staff are then given senior positions in pharmaceutical companies.
I'm sure it all works out in the end!
> There is no great interest by business in a cure to this or that
Of course there is. Cures make billions.
This might be a conspiracy theory stupider than flat Eartherism. It requires not only every Western pharmaceutical company’s collaboration, but also every one in every other country, and also all the public labs, and every world leader and their families to suck it up for the conspiracy’s sake.
Treating diseases makes billions forever curing those disease makes billions once.
Which option is selected in a capitalist society?
Goldman Sachs analysts agree with me!
https://m.youtube.com/watch?v=2m-u4cr3fJ0
Most people act against their conscience pretty much every day for money, more so in senior positions. That money is a great motivator is not really a conspiracy.
Go beyond the YouTube video reporting on the report's title and you'll find a thoughtful paper on drug pricing. TL; DR Sick people and governments will pay a lot for cures.
> Most people act against their conscience pretty much every day for money, more so in senior positions
This isn't about conscience, it's about greed. Cures are great business. Also, again, rich people get cancer. If you want to come up with healthcare conspiracies, don't pick a disease the rich and powerful get.
Blame the FDA. It is near impossible to get these treatments out to patients.
Are you not aware of the FDA’s Investigational Drugs program?
Can other countries conduct trials for these treatments at the patient's own risk?
Trials? No. There are various other countries you can go to in order to have these unapproved treatments performed, at great personal cost because there are no economies of scale. But there largely aren't countries performing trials that would count as an FDA Phase II or Phase III trial.
> at great personal cost because there are no economies of scale
I didn’t realize the USA was the only Economy of Scale
The US is the Primary economy of scale as it is the primary economy in general.
I’m talking about treatments that aren’t approved anywhere.
You specifically mentioned the FDA as being a problem; are you suggesting that approval in general is the problem, and no approval should be required anywhere?
i find this funny. what do you mean "patient's own risk?"
that has always been the case. you go for a minor surgery, you sign a waiver. you go to a doctor, they are supposed to give reasonable care. No one can guarantee success. the same with lawyers or drivers or mechanics or technicians. basically anytime you go to someone for assistance, they can't guarantee anything. the person is themselves always responsible for everything.
Of course there’s always some risk with any drug or medical procedure. But - obviously - not all risk is equal. Unapproved treatments are riskier because they haven’t been proven effective, and they haven’t been well tested for side effects. There is an uncountably large list of cases throughout history of people willing to sell ineffective and/or actively harmful treatments, which is the whole reason the FDA exists. Look up people who died taking ivermectin for Covid [1], or just pick any ailment and do some research on fake treatments, perhaps cancer for example [2]. The UN says half a million people in Africa alone are being killed every year by fake medicine today, currently [3].
[1] https://www.unmc.edu/healthsecurity/transmission/2023/03/14/...
[2] https://en.wikipedia.org/wiki/List_of_unproven_and_disproven...
[3] https://www.un.org/africarenewal/magazine/february-2023/fake...
History is also full of examples of treatments that do work under unknown (at the time) circumstances and were standardized into common practice through trial and error. This includes most over the counter medication and procedures today.
Most of that advancement stopped with the introduction of the FDA and its equivalents in other countries.
The story of efficacy trials falls apart when you consider the complex reality of the human body and pharmaceutical action. There are many medical procedures and drugs which we know work on certain patients some of the time, but we are prevented from giving to new patients because the high standards of Phase III efficacy haven’t been met.
So what? The U.S. food and drug laws aren’t protecting against things that accidentally work, they are protecting against things that don’t work. These laws are hard won and represent many people lost to both ignorance and greed.
If something has efficacy, then trials will eventually prove it, it’s just a matter of time. You just made a case that the process works. If efficacy can’t be shown, then it’s very risky for people to try the treatment, riskier than using something with known outcomes, and potentially riskier than doing nothing at all.
Either way this is all irrelevant to your bogus claim at the top that the FDA has anything to do with the perception that treatments aren’t improving. The top comment’s hypothesis is incorrect, which adds to the multiple reasons your proposed explanation is wrong.
With the FDA rules they are not legally allowed to offer such services, however.
Not sure what you’re talking about. In general the FDA does not regulate medical “services” or procedures.
Inducing ketogenesis whose byproduct is the retention of water and generation of ATP has historically acted as an epiphenomenal method of apoptosis. Survival rates vary but fasting has proven to be an effective method.
A ketogenic diet or a strict fasting regimen are two health strategies that are too frowned upon, still, and unfortunately so. Food (or whatever passes for "food" in modern times) has become such a crutch, and people have such potent emotional ties to it, that the sole idea of restricting one's diet will come across as negative from the get go. Nonetheless, there have been advancements in that regard, culturally, I believe.
Apparently I'm an incredibly healthy individual - just had a physical that stated that. I do have a good genetic base but in general I don't live a particularly healthy lifestyle, my activity is pretty much the same as everyone else - except my diet.
I'm a vegetarian and a celiac (no gluten) so I don't eat a lot of processed food. Rice, oatmeal, corn tortillas, black beans, cheese, hemp hearts, flax seeds, chia seeds, Sriracha, coffee w/honey and hazelnut creamer - all that is easily 90%+ of my diet. I also drink a protein drink called OWYN daily.
About once a week I'll have a little to eat in the morning and then I just won't really get hungry again til really late and I'll often just not eat then and go to bed. Intermittent fasting is great. A few times a year I'll go a few days without really eating - there are so many benefits to the process. The primary being autophagy - that I sus is the reason I look so much younger than people my age.
The science of sleep radically disagrees with the next thing I'm about to say.
The process with food and the body is very similar to the process of sleep and the brain.
Occasionally pulling an all nighter playing video games (can't be a stressful all nighter) is actually good for you - it resets some stuff in your head. This can be particularly effective for dealing with certain states of depression or melancholia.
Hopefully it can help people with Sarcomas.
My partner was diagnosed with stage 4 sarcoma about a month ago and life as I know it has been flipped upside down.
Firstly im so sorry to hear this. I can completely empathise as i lost my father who was my best friend to Pancreatic Cancer. Like you, one day we were fine and joking, the next day my world collapsed with the news. Uncontrollable sadness, then anger, then desperation and the why me / why my dad. I just wanted to write to you to say that you are not alone. You dont know me, i dont know you, but i wish you and your partner well and send thoughts and love. It is a surreal thing to happen. I remember looking at other people living their regular lives smiling and laughing and thinking, how can they be happy. An unbelievable amount of varied emotions. Seeing really unhealthy people, or bad people on the news, and i know this sounds bad, but wondering, why us, why not them. Just mind spinning type stuff, a plethora of every conceivable emotion. I hope you have loved ones you can vent and talk to. Again, you’re not alone.
Thank you. I can relate to everything you're saying.
I think what's been helping has been reading about death and what that means and potentially feels like. I think part of the issue is that the topic of death is so misunderstood and feared, that it creates no reasonable way forward mentally. So hopefully I can learn more about that over the coming weeks.
I'm so sorry. We all hope for a magic formula, but even with clinical trials, bench-to-bedside takes years.
>> the chimeric compound killed only diffuse large cell B-cell lymphoma cells
It's been a very weird 6 weeks. It's like, everything was fine. We had our normal suburban life. Things were going great. We had just celebrated our daughter's first birthday.
Then it's like, you realise that everything you had imagined over the next 40 - 50 years is suddenly not going to happen anymore, and it just feels so surreal.
Thankfully, a lot of the initial hysteria is gone. But there's definitely a sense of "why me?"
Sorry about your partners disease. Learning such news about loved ones is difficult.
I have a chronic condition and spent years wondering "why me?". Now my thoughts are more like "why not me?" and to try and embrace what life we're lucky to get and live day by day. Godspeed
Thank you. Did any readings or practices help you?
Regardless of your religious background, the Book of Job is deep, and sort of boils down to “Why not you? There’s much you don’t understand”.
I myself became Eastern Orthodox about 15 years ago, which has a somewhat different view of death than Western European Christianity (1). There’s also an acceptance that death occurs and that we prepare for it in our hearts, while still believing that death isn’t “natural” state. It’s a dichotomy of beliefs, but helped me accept both the reality of death but a hope for more. I pray and also love the funeral prayer in Orthodox Churches of “may their memory be eternal”. Very beautiful.
I also find the Stoic philosophers (Marcus Arelius, Epictetus) to hold to an acceptance of death and similar views of preparing oneself for it as Orthodox do. They discuss the concept of “memento mori” (2) which plays a big role in Stoic Philosophy. They focus on directing one’s internal emotions to gratitude of time with loved ones and settling anything weighing on your heart, if I understand them.
At the end of the day, both focus on preparing ourselves to realize we can die any moment and really don’t have any “right” to life. That it’s better to view each day as such and to find gratitude and peace with loved ones while you can instead of focusing on ourselves and expectations of life. We can and should feel sad and disappointed but also to not become lost in it.
Apologies for the poor writing. I’m writing on my phone and well it’s a hard topic. My mother passed away last year way too young and there’s always a feeling of loss.
May you find peace friend.
1: https://www.oca.org/orthodoxy/the-orthodox-faith/spiritualit... 2: https://www.stoicsimple.com/stoicism-death-facing-fears-of-m...
Time slows down. We spent our lives week by week. I was her care taker and hope-keeper, and I would share oncology news like this with her to help keep our family sane. I think it helped.
The "why me" for others is the first time they realize they have a chronic illness, that sudden realization that the universe is an uncaring dance of atoms, the realization that every attempt at ordering it's just a house of cards, including our DNA and everything else we rely on. I was expecting myself to land that line of reasoning into some comforting words but I have failed miserably ha, hold on tight.
“There is no justice in the laws of nature, no term for fairness in the equations of motion. The Universe is neither evil, nor good, it simply does not care. The stars don't care, or the Sun, or the sky.
But they don't have to! WE care! There IS light in the world, and it is US!”
― Eliezer Yudkowsky, Harry Potter and the Methods of Rationality
I don't like this quote because it suggests a sort of separation between ourselves and the universe, or it suggests that the universe is some all-powerful omnipotence that might deign to heal us if only we could supplicate ourselves to it, but that's mistaken.
We're made of all the same stuff as those stars. We are the universe, and if we care, that means the universe cares as well. When we have the power to do something, that means the universe has the power to do something.
Mattigames, there is a logic flaw in your little aphorism that seems quite telling. Since you and I are part of the Universe, then we would also be indifferent and uncaring. Perhaps you forgot, mattigames, that we are not superior to the Universe but merely a fraction of it.
Strange: the New York Times wrote about this on July 26, 2023.
https://www.nytimes.com/2023/07/26/health/cancer-self-destru...
That describes a related but previous Nature paper from the same group, whereas this is referring to a more recent Science paper.
The next challenge is getting the protein in there.
I love these headlines
Using prions to destroy cancer, pitting one cosmic horror against the other. Nice.
I feel like I’ve heard this before, is this something that is actually novel?
Hard to tell. The cynical response is that the novelty is that it's coming from Stanford. The perhaps more correct response is that the novelty is the mechanism of triggering the apoptosis and the specificity.
Here's a paper from 2018 that discusses the prospect of using apoptosis for cancer treatment. They even talk about BCL-2.
https://pmc.ncbi.nlm.nih.gov/articles/PMC5855670/
Triggering the automatic cell death on demand, instead of a period of time, i.e. apoptosis, sounds pretty smart and novel.
After 7 years all of our cells die and regenerate, but using biochemistry and some endogenous proteins glued together to control that period of time, i haven't heard about it before.
Not a medical expert, but cancers have a vast number of variations in the type of the cancer cell they create, but one common characteristic of all cancers is that they are derived from our own cells. So they should respond to some "commands" our own cells follow.
Inducing apoptosis for cancer prevention and treatment is old news though. Fasting, water fasting that is, causes apoptosis of cells en mass and has proven to be very effective in minimizing radiotherapy or chemotherapy sessions, and even a total treatment. Instead of doing 20 chemotherapy sessions, reducing it down to 1 or 2 and the cancer is gone.
Anyway, someone doing the same using a biochemical pathway and light up gene expression, is pretty novel.
I think you’re overstating the “proven” effect of water fasting. That said I’m surprised and happy to see that several academic medical centers are running trials of fastingin conjunction with chemotherapy.
https://www.cedars-sinai.org/discoveries/fasting-as-next-ste...
I meant "proven" when done by the patients themselves, not by the doctors necessarily.
Dr. Gundry has done an interview with a martial arts guy who was diagnosed with cancer, and fasted for 20 days only water, and 20 days a little meat and nothing else, and one or two sessions of chemotherapy or radiotherapy later he was clear of cancer. There are many people who talk about same experiences, from the patient side.
If some doctors are seriously researching fasting and cancer treatment, that's going to produce some measurements instead of relying on anecdotes.
I cannot find Gundry's interview, it's 5 years old something like that.
You’ll find anecdotal “evidence” for all sorts of stuff when it comes to cancer. Some of it is just woo, others might just work for really specific genetic mutations, etc.
Fasting in general has been known for quite a while but (and I’m far from an expert) it only helps with certain cancers. Hell, I had a friend die this year from stomach cancer and he literally couldn’t eat or drink. He only went to the hospital when he was already skin and bones, got a few chemo treatments, and then it was too late.
It’s due to the phrase “self destruct.”
For some reason people who write headlines like using this in the context of cancer cells.
First noticed it in 2010 when I was researching multiple myeloma treatments for my father.
It’s medical clickbait.
Isn't the phrase "self destruct" just meant to be a popular term of referring to apoptosis or programmed cell death in general?
When can this be used to cure prostate cancer?
Wonder if the study is freely available without paywall.
Sci-hub.pub
Is this still working? Am I being blocked at the ISP level?
For me sci-hub.pub opens a simple page listing other sci-hub URLs, but each and every one of them fails, ending in "Unable to connect" as if the server did not exist. (Tested: sci-hub.ee, sci-hub.ren, sci-hub.ru, sci-hub.se, sci-hub.st, sci-hub.wf).
Is sci-hub still working for people, I haven't been able to use it for a while.
edit: Wow, it works if I go there via VPN… incredible. So sci-hub is illegal in France?
https://en.wikipedia.org/wiki/Internet_censorship_in_France#...
This seems too straightforward to be credible? If I was researching in this field surely this is the first thing I’d try?
If it is indeed credible … this sounds like the “CRISPR moment” of cancer treatment, sure. And I’m really happy for that.
But I will be honest and write what I’m thinking: if this is real then frankly I’m disappointed it took this long. Do we really have our best people working on cancer? I have known so many who died waiting.
It seems like there has been roughly the same investment this decade (around $200B) in climate tech compared with cancer research, and yet electric cars and batteries are now a “solved problem” that’s just waiting to scale. The progress with Cancer is noticeably less. Is the money being well spent? Or are we donating $100B-s for researchers and labs to sit on a gravy train making sub tier progress.
Here’s a wild theory. Perhaps as a society we built the wrong prerequisites to get into cancer research and we filtered out all the Mozart’s and Leonardo’s…
I work in this area.
It took time to know what each protein does in a cell (we still dont really understand most of them), it took time to find all the ways that various cancers use the protein machinery in the cell to their benefit (new ways are still being discovered these days), it took time to think about molecular glues and turn them practical, and it took time to build the right chemistry and then test it (it takes time even after you know all of the previous steps.) It will still take years, possibly over a decade before this particular development can lead to a drug that passes human clinical trials and is eventually approved. It is not the lack of geniuses that slows things down, rather it is the very careful consideration of risks to minimize the loss of human life during experimentation, and the attempt to optimally allocate the resources across too many different challenging problems in order to maximize the long term benefit to society. The true amount of money spent in cancer research is much higher than the $200B over a decade that you mentioned, however the vast majority of it is just capital losses of various companies spent on the tools and research in early stage discovery across tens of thousands of projects, and a separate huge and more obvious chunk goes to attempts and failures at human clinical trials. The cost of drug discovery has stopped increasing exponentially during the last decade but is still pegged at several billion dollars per approved drug without counting costs from competitors who never get anything approved.
> If I was researching in this field surely this is the first thing I’d try?
Let me ask a clarifying question: Are you saying that the first thing you would have tried is to synthesize bivalent molecules that link ligands of the transcription factor B cell lymphoma 6 (BCL6) to inhibitors of cyclin-dependent kinases (CDKs)?
Or are you just saying that you would have tried to drive cancer cells to self-destruct (but have no clue how)?
With a little domain knowledge and research you find out pretty quickly that:
BCL6 is lymphoma.
CDK regulate cell death, amongst other things.
So yes, I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present.
It seems hard to believe that it is presented as novel with the amount of funding that has been spent on cancer.
> With a little domain knowledge and research you find out pretty quickly
That's cool. Where do you think that domain knowledge comes from? Did we just found it in a fortune cookie? Or does the cancer research conducted has something to do with that we have this knowledge?
> BCL6 is lymphoma.
That's not correct. BCL6 is a protein, or a gene which codes that protein. Mutations in BCL6 can lead to B cell lymphomas. BCL6 is not lymphoma.
> I am saying that it seems very straightforward as an approach to attempt to trigger a CDK cell death when BCL6 is present.
Excellent. Sounds like you are an oracle of oncological research roadmap. What should be the next target to develop drugs for?
I am glad that you know these things, but cancer research has still failed society as a whole.
3 of my immediate family have had cancer, 2 took chemo and it ruined their lives (it caused weak bones, their spines to virtually dissolve, which led to surgeries to insert plates and things, which have failed multiple times, it has been a mess).
The third was not eligible for chemo because they were too sick and they had an existing case of lupus. So we started trying things -- probably 100 different things at first. What worked for them is taking Sanguinaria canadensis daily orally. It is now 15 years later and they still have cancer but are living a normal and healthy life.
You know, despite being the most effective treatment you could possibly hope for in this situation (besides an actual cure), there are only a few papers on Sanguinaria canadensis, and most research discredits it. Other friends of mine have tried chemo and died in a horrible way. Now you understand my criticism of cancer research. For all the money that has been spent, the most viable treatment available through a hospital is still a living nightmare.
Current SOTA (state of the art) treatment for cancer is:
Sequence patient's tumor mutanome distribution, create personalized therapy encoding the top N neoantigens
+
Anti-PDL1 checkpoint inhibitor
+
mRNA encoded albumin-IL2
We got a cure for cancer before gta 6
I am tired of news like this that never gets anywhere. We have a billion way to destroy cells, great. Let's get a reliable delivery system working now. While that is in the works, I will stick to fasting and other simple methods of decreasing oxidative load.
As someone who tried to keep a cancer patient alive for as long as possible, this type of news offers hope, and encourages young people to become oncologists and researchers, which we so desperately need.
The entire point of this research is to develop a targeted delivery mechanism based on malfunctioning gene activations. It's a simple but clever approach IMHO.
Bought out and shutdown by profiting businesses as usual.
No, this whole spiel of big pharma wanting to keep people sick is insane. That could work if there was a single pharma company in the world, but all it takes is one company making an effective cure for a disease and they will make big bucks. Even if you think the people in charge are evil profiteers, we all win in the end