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New pancreatic cancer drug might open the door to much longer survival times

economist.com

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Re: New pancreatic cancer drug might open the door to much longer survival times

#121
post #115

Earlier quoted context omitted.

Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?

evolution is a wrong concept to approach it. cancer is not a separate life form, but a bug in the regeneration system of a complicated life form. it doesn’t exist outside of it, it cannot propagate.

I've heard that some cancers spread by viruses. Viruses do evolve. No idea if that says anything about cancer evolving.

Re: New pancreatic cancer drug might open the door to much longer survival times

#122

Earlier quoted context omitted.

Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner. One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position. This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that targ…

How does it avoid targeting KRAS in healthy cells? Or is this another form of chemotherapy where we're trying our hardest to deliver the right amount of poison that kills the cancer before it kills the rest of you?

It doesn't. Cancerous cells have a much higher dependency on RAS signaling to survive, so it's a drug that kills everything that's replicating via RAS signaling, much like standard chemotherapy kills cells in general that are reproducing more quickly.

However this is just the first version of the drug, it can be combined with other modalities to allow more selective targeting of cancer versus not cancer cells (e.g antibody-drug conjugation). And when used in earlier stage cancers, rather than the advanced cancers in this first clinical trial, there's the possibility of lower dosing that has less strong side effects.

This is just the first attack that has ever broken through to hit a key weakness of some cancers. It's the start of learning, a breakthrough that will launch refinements, enhancements, and a ton of innovation. That sort of innovation is sometimes derided as "me-too" drugs, and not meaningful, but some of the biggest advancements in cancer care have been from taking very hard to tolerate treatments and making them more tolerable and refined and better for patients, allowing longer and more thorough killing of cancer cells. I would expect we will see a lot of that here, as well as work towards combinations with other drugs.

Re: New pancreatic cancer drug might open the door to much longer survival times

#123

Earlier quoted context omitted.

Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner. One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position. This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that targ…

> Cancer is not one thing, I know this is a popular "well actually" to do, but it is not always useful in a conversation. Yes, all cancers are different, but yes, cancer is also one thing: unchecked, harmful division of cells. Bacteria are also all different, but still they are "one thing", and despite their diversity, antibiotics exist that can deal with many species of them at once. It is reasonable to talk about b…

The correct way to read the sentence is “all cancers do not have the same causal mechanism” but people don’t talk like that because it’s off putting. Language is fluid and it’s generally on the reader to infer meaning from context. If we can do so reasonably, we do it, and we don’t need to then write additional posts chiding people over an interpretation that’s highly unlikely to be the intended one. I don’t mean to be pushy about this, btw. It’s just that pedantry can be valuable, but only if it isn’t abused.

Re: New pancreatic cancer drug might open the door to much longer survival times

#124

Earlier quoted context omitted.

Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner. One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position. This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that targ…

Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?

Absolutely, this is selective pressure at work on cells with malregulated genetics. Most typically, this is in the form of drug efflux pumps, but you can definitely get more specific resistances.

Ways to avoid specific resistance include multiple treatments simultaneously, since the probability of generating resistance to both is the product of the probability of resistance either.

Re: New pancreatic cancer drug might open the door to much longer survival times

#125

Earlier quoted context omitted.

Cancer is not one thing, it's a huge zoo of many many many ways that cells start to break the social contract and divide in an uncontrolled manner. One of the most commonly observed broken mechanisms is mutation in the gene KRAS that turns this on/off growth switch into the permanently on position. This has been known for decades, of course. And there have been huge amounts of effort to try to develop drugs that targ…

Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?

Yes, and one of the hallmarks of cancer is a removal of the usual DNA damage checkpoints. Cells have sensors that detect damaged DNA and stop cell division, and once that is gone evolution happens on an extremely accelerated times scale. In lung cancer, for example, we have developed entire series of drugs to go after successive resistance mutations inside the EGFR gene.

When we first started getting good at sequencing the DNA of tumors, I remember initial reports of taking samples across the 3D space of a tumor and finding great spatial heterogeneity in the tumor genomes.

I'm actually most excited for using this drug in combination with colon cancer, where KRAS mutation is a common drug resistance evolution in response to drugs that target the gene EFGR (though cancer researchers may all have their favorites to go after, colon cancer went after my family especially hard).

Re: New pancreatic cancer drug might open the door to much longer survival times

#126
post #115

Earlier quoted context omitted.

Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?

evolution is a wrong concept to approach it. cancer is not a separate life form, but a bug in the regeneration system of a complicated life form. it doesn’t exist outside of it, it cannot propagate.

Cancer researchers generally refer to it as evolution, and I've never heard any complaints from the population geneticists or evo-devo folks about it, so I don't think it's a tremendously controversial way to talk about it. See for example

https://www.nature.com/articles/s41586-019-1907-7

Re: New pancreatic cancer drug might open the door to much longer survival times

#127

Earlier quoted context omitted.

Everyone dies. Dying 5 years later is a victory. I would go so far as saying if it was you or someone who you care about you would understand. https://usafacts.org/articles/how-have-cancer-rates-changed-... >However, even though the overall number of cases rises as the population grows, fewer people are getting and dying from cancer. Between 2000 and 2021, the incidence rate — or the rate of new cancer cases per 100,…

Unfortunately in this particular case people die about 6 months later, not 5 years. See the article.

This is just a failure of understanding. This particular advancement is part of a decades long slog which taken together allows a substantial number of people to live meaningful additional durations every single year. 6 months average by itself means that John got another 3 years even if Jane only got 3 more days.

If I pulled one person out of a burning building it would be newsworthy. Doctors are and have been pulling train loads every day.

Re: New pancreatic cancer drug might open the door to much longer survival times

#129

Earlier quoted context omitted.

But that's not a cure. If they don't take that drug, assuming it works, they still have the original mutation in the cancer cells. > Patients that take part in clinical trials really are the heroes here. Are they? To me personally, putting people into a permanent state of requiring drugs to survive, is not really cure. It's just maximizing income for those selling those drugs. And none of those drugs work exceedingly…

I can understand being frustrated and cynical with the pharmaceutical industry, but I have never worked with a single doctor that approaches patient care with the goal of getting them "hooked" on something for life. The pharmaceutical companies are not the ones making clinical decisions - in this case, it's a shared medical decision between a patient and their oncologist. Having seen how horrific pancreatic cancer is…

Pharmaceutical companies do make clinical decisions, it just isn't called a clinical decision. But they decide what research to pursue, and thereby decide which drugs exist for the doctor to choose.

Re: New pancreatic cancer drug might open the door to much longer survival times

#130
Horrible disease. We just buried my wife’s father because of stage 4 pancreatic cancer. A month ago, he was still living his life as usual. Then he developed abdominal pain, was diagnosed, and died three weeks later.

I think we should also invest more in better diagnostics and early cancer detection. That could save many lives too.

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