Every little step in fields like this is so encouraging. We keep getting better, but the cancers don't.

Ever more effective cocktails of drugs that target the cancers while minimising harm to everywhere else, the closer we get to attacking cancer cells from so many different directions they simply can't adapt in time and we wipe it out immediately (a cure). One can only hope.

I whether we might see even more investment into research like this as it gets closer to deliver curative, rather than just suppressive outcomes, as well

CAR-T may have a ~50% cure rate for blood cancers: https://ashpublications.org/blood/article/141/19/2307/494672...

My uncle underwent CAR-T therapy and the turn around was amazing. He's got a brand new lease on life. We would have lost him without it.

What disease did it address?

> whether we might see even more investment into research

The field would benefit greatly from even a fraction of the investment in the AI and crypto bubbles

Cancer research is a massive, massive industry, with multi billions of grants on the line for every foundation and lab that cares to stick their fingers into it.

The only thing that could ruin the cancer industry and dry up the firehose would be finding cures or reliable treatments that healed human beings, rather than making them sicker, impoverished, and/or un-alive. That would surely spoil everyone else's party.

Suppose for one second that all these people are profit motivated. Whatever research money there is, there is far far far more to be had for the patent royalties from treatments.

Not even close. So much more money to be made from treatment than from research. And there is so much money to be had from beating a competitor with a better treatment than there is to have an equivalent treatment

Taking a cynical profit-only driven view of the world would optimize for better cancer care.

But nobody goes into it "aha I want to make a lot of money." They might go into it wanting to get famous for coming up with a cancer cure. But take the cures that are most closely associated with individuals, whether it's a drug targeting BCR-ABL1 fusions or HER2, and almost nobody knows their name. So even then the fame motive is pretty weak.

> Taking a cynical profit-only driven view of the world would optimize for better cancer care.

There are many promising research directions, which are however grossly underexplored, either because there is a low chance it might lead to a positive result, or because it cannot be patented even if it's successful. Examples in the latter category include off-label use of established procedures, or of already known drugs. Conversely, the majority of money and energy is being spent on highly predictable research and which can result in a patent; almost always the downside is low impact. So as you can see, profit optimisation is not correlated with impact optimisation.

Calling off-label repurposing of established drugs "under explored" is a bit insulting to all those people that attempt it all the time, without a higher success rate than any other method. Folks like Razelle Kuzrock make great progress, and the "under exploration" is more about not spending enough time exploring RNA or protein diagnostics rather than DNA diagnostics, if anything. Which isn't due to lack of impact or profit optimization, just due to intuition biases of the field.

Calling profit and impact optimization "uncorrelated" is not justified by your comment. The biggest impact in the past decade of cancer has undoubtedly been immunotherapies, which are also by far hugely profitable. And immunotherapies themselves were often a backwater, far more so than drug repurposing, until the impact came through with a patented drug.

Good to see a shoutout to Kurzrock!

I don't believe this even in the most charitable reading.

Some people are convinced that healthcare initiatives are so corrupt as to be theater, in regard to finding new treatments, somehow forgetting that the competition is measured on a race to the highest survival rating (both in large populations and small populations looking to grow - ie Israel). Billions of dollars is nothing if you have billions of people paying even 20$ a month for the duration of their extended lives, going forward through history (since cancer wont stop). It's a purile fantasy that their is a cabal of mustache twirlers, sabotaging medical discovery.

Do you know what motivates hedges to fund new startups effectively? Success in previous investments. Drug cures have nothing but upsides for every economic strata.

Except there is an overabundance of historical evidence of hedge funds giving almost exclusive preference to research which is highly predictable and has negligible impact, as long as it can result in a patent.

See for example below. Aging research is one of the most eclectic areas, because it touches on virtually all biological systems. There are countless promising directions which are grossly underexplored. Yet this massive hedge fund chose to invest in discovering new analogs to older drugs. Why? Because the older drugs are effective, discovering new analogs is easy and the patented products can then be marketed.

For general overview of the fund: https://www.technologyreview.com/2022/06/07/1053132/saudi-ar...

Their first major investment was in analogues of a decades old drug called rapamycin: https://www.hevolution.com/en/web/guest/w/hevolution-foundat...

So, yes. There is a provable cabal of mustache twirling investors who optimise for profit, at the cost of impact. Why you would defend them, in spite of your self-professed rational interest in the positive externalities of revolutionary healthcare, is beyond me.

Funding in addition to not to the exclusion of. People still fund new restaurants and strip malls not just startups.

Closely related drugs may not cure new diseases but they do help. There’s a lot of drugs like Morphine but the thing is that give doctors options for better treatment. Fast acting and fast metabolizing is beneficial when an EMT is helping someone deal is massive trauma, post surgery recovery and you want a different drug.

Cialis and Viagra may both make your dick hard, but millions of people benefit from the options from having both.

Funding is the essence of scarcity. Funding one thing means those money will not be funding anything else. But you're free to be content with countless minor variations on existing treatments [0]. Curing cancers will require an actual breakthrough.

[0] https://duckduckgo.com/?q=capitalism+breeds+innovation&t=fts...

Total funding for all human activities is scarce, but can go to anything. Money spent on video games could instead be used to fund cancer research.

Thus the percentage of that funding going to medicine isn’t fixed. We essentially spend extra money on this kind of research rather than diverting cancer funding to look for new pain medications. Further, people with sage IV cancer really have benefitted from better pain meds it’s not as useful as a cure but it’s still useful.

Capitalism has freed 90% of humanity to do something other than farm food. We’re in the 3rd stage of human history first almost everyone was hunter gatherer, then nearly everyone was farmers, now people do all kinds of things. How we spend that seemingly boundless surplus of labor may not seem efficient, but it doesn’t need to be to be dramatically better.

Progress is exponential. So looking in the past and saying we should be content with a 90% improvement is misleading, because it is dwarfed by how much more potential there is.

That exponential is based on the increase in number of people not farming. Graph the number of writers/scientists/engineers/etc over time and it’s an exponential, but population isn’t expanded exponentially any more.

The free ride feedback loop is ending very soon.

> Why you would defend them

I don't defend "them". There is no "them". Conflating price gouging with lack of agency is, a different issue, outside of research. Patents count as output. Regulation hinders progress in the interest of safety and accountability. There are tradeoffs, granted. The idea that funds want to fund partial cures, rather than more comprehensive ones, is partially true. Comprehensive would be better for everyone, if it wasn't so damned difficult in western nations.

PHDs are predicated on thesis papers to prove something novel, which largely have no impact on society. This is a consequence of knowledge availability (and consequently utility), not maliciousness. Medicine is not special, in this regard.

The survival bias applies here. It's hard to know the diseases that are cured or have new treatments, because those cease to be issues at the forefront. Onchocerciasis? Nobody in the 1st world cares that was cured. Peptic ulcer disease? That was handled. What about medical procedures? Even incremental improvements to drugs, allow for more effective treatments or old treatments to have significant efficacy increases.

GL with whatever.

That’s good, because it’s total nonsense. There are many things that hold back cancer research, but this story of conspiracy is not one of them.

Cutting edge pharma companies, believe it or not, have an incentive to cure cancer. Even from a naive supply and demand argument it makes no sense.

To be fair, dead and dying people are pretty bad at paying bills. Even assuming staggering, unrealistic levels of corruption in all parts of healthcare, someone in the chain ought to be financially motivated to see the patient recover.

Indeed, the medical system has a vested interest in not un-aliving people, and enforcing customer loyalty, and having patients punching their frequent-flyer cards.

It's important to play a long game with healthy people, and to find very minor conditions which can be medicated with very weak doses. So the intial treatments are really tests of obedience and loyalty, and the credulous patient begins the rituals and sacraments which will, ostensibly, keep them alive, manage their symptoms, and most importantly, keep coming back for more tests. (Because there are never fewer tests once some diagnoses are handed down. There are always more tests, more screening, more monitoring, and the goalposts move closer every year, such as the AHA's hypertension criteria, or the DSM's ever-widening net to catch mental disorders.)

And it's undeniably true that the companies who manufacture DDT, Agent Orange, mustard gas, birth control, formaldehyde, fluoride, X-ray and CT machines, should have a vested interest in curing cancer. Who could deny that.

I'm also quite confident that the FDA and the DEA would be champing at the bit to approve any substance or device that could diagnose, treat, heal, or cure a disease, that they would readily accept any and all existing evidence for those cures, no matter how old or foreign, and that they would be eagerly fully endorse, and even subsidize, the distribution and sales of said substances as much as humanly possible. Because the FDA and the DEA exist to make Americans as healthy as possible, and live as long as possible, reduce the demand for drugs in society, and hold off the moustache-twirling capitalists who dare to conspire against us!

And of course Israel wants to grow. Israel can grow faster if they can perpetrate genocide against all the Arabs there. And likewise, Palestine can grow as soon as they murder enough Jews who live alongside them. So there's growth and there's growth. https://youtu.be/aHVx4nqgMPQ?si=jMgUWRvOsTUZJbNn

Chemotherapy is really just the end-game where the patient has been drained of all resources and the death panel has spoken. Chemotherapy is the ultimate test of that loyalty and obedience: "We propose to poison you to death, or to within an inch of your life. We'll systematically destroy every organ, every bodily function, and every ounce of your will and resolve. You'll lose your hair, vomit, feel horrible, and you'll genuinely wish for death. Continue? (Y/n) "

Of course, many elderly patients do not die of chemotherapy, but if you are loyal and obedient to your physicians, eventually you'll be on mind-boggling cocktails of medications. I have seen people managing dozens of them at a time. Rolling up to pharmacies with a forklift and a blank check. Programming a spreadsheet trying to make sense of them all. Fighting their insurance tooth and nail to get paid. Taking medications to counteract side effects, and medications to counteract those medications. I mean, even the PCP can keep this up for decades. And the PBM just eats it all because it's "Medically Necessary", until all the side effects sort of swirl into a synergy of horseshit, but some voice of reason gently whispers "hey, why don't we cut everything to zero and start from scratch?" and the patient has somewhat of a miraculous recovery, because they were dying from drugs, not from disease.

Wow, this looks exactly like a sign of a mental illness and/or a bad LLM.

Or it looks like someone suffering from the effects of healthcare treatment of loved relatives, looking for connections and a narrative that fits what happened to a tragic event. Within that cynical diatribe lies a narrative that resonates with some.

That narrative can be boiled down to: Profit in patient treatments produces perverse effects.

It's an alignment problem, where profit aligns to treatment over cures (a metaphor is the overreach of SaaS solutions when more static software could do).

In other news: hunger is caused by farmers.

supply chains logistics, capitalistic urges to throw out food instead of giving it away, zoning and HOA's preventing home gardens, coordinated rental hikes, none of those things are aligned with feeding people but instead aligned to bilk money from peoples' hunger (or shelter in the case of renting).

The farmer is relatively aligned financially with feeding people by comparison: they are paid money to grow food...

I don't understand your point or comparison.

Pfizer acquired Seagen for $43 billion. Seagen has some very promising ADC’s in the queue.

https://www.pfizer.com/news/press-release/press-release-deta...

It's weird to think of a hopeful story of a $43Bn acquisition.

My dad (retired) spent the back half of his career working on ADCs at Seagen. He's glad ADCs panned out as useful cancer treatments.

> The Food and Drug Administration approves new cancer treatments when they are shown in clinical trials to be more effective than the current approved cancer treatment for a given cancer type. The approval comes when the treatment extends lifespan without overly increasing the risks of serious side effects.

This standard just doesn’t make sense to me. Every case is different, so why “throw out” a treatment option for only being within the margin of error of efficacy on a general population? It must be incredibly frustrating for patients to know about these treatments…

It's fine to ask for an approval for a part of the population (e.g. people with cancer exhibiting particular markers).

Never let a customer off the hook too early

The issue with ADCs is you're putting a really giant homing system on a tiny warhead. How many molecules of X does it take to kill a cell? There is one really good warhead candidate, but un?fortunately it's illegal to research

What candidate are you referring to?

Nope. Don't want to be on surveillance lists, even with an anon account. Was researched in the 80s, before we knew enough about the antibody side to make a good go of it. then dropped for obvious reasons (it didn't work which makes sense in retrospect given the crude conjugation strategy plus the restrictedness of the warhead side). That's all I'll say.

Probably enough info for you to figure it out if you're smart. Don't wind up in jail.

Are you referring to monoclonal antibodies? For which a Nobel Prize was awarded in 2018, and research has continued since the 80s?

No, that's the "homing system" side of this analogy. GP is talking about some sort of poison (chemo), but I don't know which one or what the paranoia is about.

Yeah there's stuff that will get you on lists especially since 9/11. But some of them have been restricted since before that, though de facto unenforceable. Today there is the ability to ingest huge volumes of data. I just don't want to deal with the pain in the ass even if I'm found innocent.

Your paranoia is not justified. merely mentioned potential treatments (even ethically questionable ones) does not get you on any "watchlists".

Just say what it is you're referring to, or don't mention it at all.

I will do this for you. List 20 compounds surveiled by the US government for potential association with terrorist groups in a comment under your account below this comment and I will answer yes/no if it is in the group as a whole.

Merely mentioning illegal/regulated drugs does not get you on a watch list. Answering yes/no to a list does not protect you. I will not continue to engage.

That's fine if you don't respect my boundaries I don't need your engagement

I remember reading somewhere that doctors are experimenting with (or wanting to) some of these more modern treatments first. Right now they're all "exhaust your other options, and then try the new stuff as a weapon of last resort". The more modern treatments could be more effective if we try them first instead of waiting, but we just don't have the data.

Anyone have a source on this half-recollected fact of mine? I can't find one.

Anecdotally, I can support this.

A loved one is moving through this pathway now. Its has you said: try all the established drugs first, even if they aren't directly indicated for the cancer diagnosis of the patient, then move on to the more modern and specific treatments once the established medicines have failed.

One problem with that approach is, once the patient has reached the point of several failed treatments, the cancer has possibly become advanced and the patient is worn down by the earlier interventions. In my observation, this confluence makes the newer medicines simultaneously harder for the patient to tolerate but also appear less effective than might've been the case at earlier stages of the disease.

My wife, now deceased from MBC, took two ADCs that had the same payload (chemo) but two different antibody signatures. The first one did great for about 3 months. The second one failed, major progression. But the conclusion was still unknown, what information did that give us? Was it the cancer rejecting the antibody or mutating to overcome the chemo effects?

Tools we need (large scale):

- how can we identify when the cancer mutates, what part of the ADC is it rejecting? This information is valuable.

- how do we assign different payloads? Can this be scaled? Do new payload/antibody delivery systems need to go through the FDA each time? How do we streamline this to add a wider net to catch cancer mutations?

You can do blood tests to catch cancer mutations, used presently. Many blood tests.

It can be a cancer mutating. It can be the cancer not mutating (occurs after drug given) but is mutated (mutation occurred already). We have a population of a billion cancer cells. Treat with drug. 999 million die, 1 million survive because they had that mutation conferring "fitness" i.e. resistance to drug. three months later, we have a billion cancer cells again, descended from the 1 million cells. Now those billion cells also get the next line of therapy. 999 million die, 1 million survive. 3 months later, those 1 million are now a billion again. And so on. Point being, I'd think of it more as a selection mechanism as Darwin taught us, not the cancer automatically generating a resistance mutation - the blind watchmaker. In this case there was probably a mutation changing or downregulating the antibody target, probably HER2 or something related.

I don't know what "rejecting the antibody" means. You would need to look up the ADME to understand physiology and think about how the cancer might modulate that.

All this talk of "oh how do we catch these mutations".. ... ... there are a few dozen companies that will tell you what mutations are there straight up, just from the blood. From the tumor, any hospital can tell you all the mutations. The problem isn't that we don't know. We can tell you the mutations. We can tell you the new mutations. So we find 100 mutations let's say. Okay. Next question, for each of the 100 mutations, does it cause resistance, yes or no? Do two of them together cause resistance? Are they from the same cell, they could be from distinct tumor lineages. You know most of the mutations are what are called "passenger mutations" right? Red herrings.

So this is the pathology of computer scientists. "If only a clever programmer took a crack at this, these biologists what with their humanities style miasmas and rote memorization topical field". Many have in fact... Bioinformatics goes as far back as the 1970s I'd say if not further. And that clever programmer did find all the mutations. Did a great job. Pretty well developed. Then you say "ah let us understand what the mutation does!" Okay. So now you're taking a subset of the broader field of genomic variation and computationally deriving how that variant influences trillions of different cells interacting with an antibody protein with a chemical bound to it. Congrats, if you're such a "clever programmer" than by solving this, you've solved life itself! Basically this notion is "this looks easy, what is this, like the 3-SAT problem, figure if someone was clever enough to take a crack at it then that would solve this whole 3-SAT issue!" completely blind to the fact that it's just as hard (and the same) as proving P=NP. So if you ARE a hardcore clever programmer, then this rabbit hole goes as deep if not deeper than P=NP, and the cancer will humble you, as this is what cancer does, to humble.