4 ms·

What does this mean in layman's terms? How will this potentially help me if I get cancer?

GaggiX 4mo ago
One of the many therapies that are being developed so that you can survive longer even with the most lethal tumours.
epistasis 4mo ago
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 target KRAS in cancer, but for decades it's always been thought of as 'undruggable' because of the difficulty of finding any molecules that would affect it. This new drug, that finally treats KRAS mutated cancers, goes about it in a new way. Instead of trying to gum up the works of a single protein by sticking a small chemical in it, it effectively "glues" the KRAS protein to another protein, CypA, which keeps the switch away from reaching the normal areas where it's "on switch" activity works. So this new drug means two things: 1) a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, 2) there's an entire new class of drug activity that everybody is chasing at this very moment, so in 5-25 years we'll likely have a huge number more of these sorts of treatments.
- oh_my_goodness 4mo ago
  >a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?
  - deleted 4mo ago
    [deleted]
  - memonkey 4mo ago
    I think the meaning is that because we can see success with KRAS mutation of pancreatic cancer, we can now begin clinical trials for other cancers that may have KRAS mutation (colorectal, lung) and see if there is success there. If there is success in treating other cancers during clinical trials, it could be fast tracked through FDA to be more generally available and then become part of the national treatment option (ideally in 1-5 years after clinical trials).
  - epistasis 4mo ago
    The next 1-5 years will tell us which cancers this new drug will work well on, right now it's only been tried in pancreatic cancer when people have failed their first treatment. The new drug from the article, daroxonrasib, has nine trials i see currently, here: https://clinicaltrials.gov/search?intr=daraxonrasib&viewType=Card https://clinicaltrials.gov/search?intr=daraxonrasib&viewType... The first two are the trial that just completed and showed success: people that have pancreatic cancer that failed other treatments, then a "trial" that is meant to give quick access to more people now that it's been shown to work. Then there's a trial for using it as the first-line treatment for pancreatic cancer, one for lung cancer (NSCLC), and also various combinations with other drugs. I expect we'll see a ton of new trials registered in the coming year. Especially something in combination with colon cancer, because a common drug resistance mechanism in colon cancer is to develop KRAS mutation. The thing is that we don't really know which cancers it will work well in until we try. And there's limited number of people with cancer that enter clinical trials, and we want to give each person their very best chance at survival, and then there's the massive expense of running the clinical trial itself, so learning happens slowly, one month of survival at a time, or one cancer recurrence at a time, or one death at a time. Patients that take part in clinical trials really are the heroes here. (Especially with the side effects of this new drug, which are horrible. It is a revolutionary drug, but we need to learn how to manage the other things it does as well, and that's going to take time.)
    - shevy-java 4mo ago
- redleggedfrog 4mo ago
  That was a really good summary, thank you.
- bad_username 4mo ago
  > 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 bacteria and antibacterial medications, it is also reasonable to talk about cancer and cancer treatment. I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).
  - dpark 4mo ago
    It seems relevant here because the question was “How will this potentially help me if I get cancer?” and the answer is “Not at all unless you get a particular form of cancer that this applies to”. > 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. Except people don’t ask “what if I get bacteria” the way they ask about cancer. If the story was about a new antibiotic that only affected 20% of common infectious bacteria strains and someone asked “in laypersons terms, how will this help me if I get a bacterial infection”, it would be appropriate to clarify that it only applies to some bacteria.
    - LoganDark 4mo ago
      > Except people don’t ask “what if I get bacteria” the way they ask about cancer. Yeah, but doctors also don't tell people "you have bacteria" or claim "we found a cure for bacteria". The lack of nuance on average is largely due to a lack of nuance from experts. The media treats cancer as one big thing and bacteria and viruses as separate things. Thus the average joe inherits 'treating cancer as one big thing' from the media.
      - jldugger 4mo ago
        Is it? I'm pretty sure oncologists will say "you have stage 2 breast cancer," but I wasn't in the room at the time.
- dyauspitr 4mo ago
  The golden panacea for this would be a gene editing mechanism that will work in every cell in the body. Once we have something we can do whole hog gene replacement, most human health problems would be solved forever.
  - tremon 4mo ago
    For every cell mechanism that's being abused by cancer to fuel its growth, there are other cells in the body for which that mechanism is crucial for their correct functioning. Wholesale editing every cell in the body mostly guarantees that the patient does not die of cancer -- the cure will kill them before the disease does.
    - dyauspitr 4mo ago
      Only cells that have the necessary signature get the edit
      - Hendrikto 4mo ago
        So the exact opposite of what you said initially.
        dyauspitr 4mo ago
        No, a mechanism that acts on every cell on the body doesn’t mean it changes every cell. The primary problem with gene replacement therapies is they cannot be effectively delivered to every cell. If we can find a way to deliver to every cell than just the ones with the right signature will get the changes.
- juleiie 4mo ago
  [flagged]
  - epistasis 4mo ago
    Are you going to give them cancer first too? This is a horrifying proposal not only on the ethics front but also in the scientific uselessness of it. This is exactly the type of thing that gave the Nazis the bad name they deserve.
    - juleiie 4mo ago
      [flagged]
      - wongarsu 4mo ago
        Until you get to the second order effects. If we want to find a cure for some disease, but we don't have enough people to do experiments on (maybe a lot of eligable prisoners died in previous trials) judges now have an incentive to hand out life sentences to people with that medical condition Even just subconsciously that would have an effect
        juleiie 4mo ago
        [flagged]
        deleted 4mo ago
        [deleted]
        wongarsu 4mo ago
        That won't create justice, only judges that forever encode current prejudices
        ycombinator_acc 4mo ago
        As opposed to future prejudices? I agree: the trials are not speedy enough. None of us will live long enough to take advantage of the endgame version of this.
- basisword 4mo ago
  Thanks for the explanation!
- inigyou 4mo ago
  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?
  - epistasis 4mo ago
    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.
  - jibal 4mo ago
    This drug targets cells with a KRAS mutation that locks the KRAS switch in the ON state, driving uncontrolled growth. Cells with this mutation are abnormal and predisposed to becoming cancer ... so by definition are not healthy.
- throwaway81523 4mo ago
  Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?
  - ulbu 4mo ago
    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.
    - 8note 4mo ago
      the single celled dog might beg to differ. sometimes a cancer can then survive on its own back as a single celled organism
    - throwaway81523 4mo ago
      I've heard that some cancers spread by viruses. Viruses do evolve. No idea if that says anything about cancer evolving.
    - epistasis 4mo ago
      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 https://www.nature.com/articles/s41586-019-1907-7
    - nly 4mo ago
      You might want to read this https://en.wikipedia.org/wiki/HeLa https://en.wikipedia.org/wiki/HeLa
  - nicwilson 4mo ago
    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.
siva7 4mo ago
It won't help... mind you this is an article from the economist. There is no such thing as a cancer "master switch", that would equal a disease master switch and that point we have solved biology.
- sarchertech 4mo ago
  What do you mean “it won’t help”? It most likely will help if you get pancreatic cancer. It might help if you get one of the other types of cancers with this mutation. And it will likely lead to new treatments for some of the worst kinds of cancer.

One of the many therapies that are being developed so that you can survive longer even with the most lethal tumours.

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 target KRAS in cancer, but for decades it's always been thought of as 'undruggable' because of the difficulty of finding any molecules that would affect it. This new drug, that finally treats KRAS mutated cancers, goes about it in a new way. Instead of trying to gum up the works of a single protein by sticking a small chemical in it, it effectively "glues" the KRAS protein to another protein, CypA, which keeps the switch away from reaching the normal areas where it's "on switch" activity works. So this new drug means two things: 1) a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, 2) there's an entire new class of drug activity that everybody is chasing at this very moment, so in 5-25 years we'll likely have a huge number more of these sorts of treatments.

oh_my_goodness 4mo ago
>a lot of the most difficult to treat cancers are now far more treatable, and in the next 1-5 years clinical trials will tell us which cancers this particular drug works well for, Can you help disambiguate this? Are there treatments now, or are there potential treatments with trials in 1-5 years?
- deleted 4mo ago
  [deleted]
- memonkey 4mo ago
  I think the meaning is that because we can see success with KRAS mutation of pancreatic cancer, we can now begin clinical trials for other cancers that may have KRAS mutation (colorectal, lung) and see if there is success there. If there is success in treating other cancers during clinical trials, it could be fast tracked through FDA to be more generally available and then become part of the national treatment option (ideally in 1-5 years after clinical trials).
- epistasis 4mo ago
  The next 1-5 years will tell us which cancers this new drug will work well on, right now it's only been tried in pancreatic cancer when people have failed their first treatment. The new drug from the article, daroxonrasib, has nine trials i see currently, here: https://clinicaltrials.gov/search?intr=daraxonrasib&viewType=Card https://clinicaltrials.gov/search?intr=daraxonrasib&viewType... The first two are the trial that just completed and showed success: people that have pancreatic cancer that failed other treatments, then a "trial" that is meant to give quick access to more people now that it's been shown to work. Then there's a trial for using it as the first-line treatment for pancreatic cancer, one for lung cancer (NSCLC), and also various combinations with other drugs. I expect we'll see a ton of new trials registered in the coming year. Especially something in combination with colon cancer, because a common drug resistance mechanism in colon cancer is to develop KRAS mutation. The thing is that we don't really know which cancers it will work well in until we try. And there's limited number of people with cancer that enter clinical trials, and we want to give each person their very best chance at survival, and then there's the massive expense of running the clinical trial itself, so learning happens slowly, one month of survival at a time, or one cancer recurrence at a time, or one death at a time. Patients that take part in clinical trials really are the heroes here. (Especially with the side effects of this new drug, which are horrible. It is a revolutionary drug, but we need to learn how to manage the other things it does as well, and that's going to take time.)
  - shevy-java 4mo ago
redleggedfrog 4mo ago
That was a really good summary, thank you.
bad_username 4mo ago
> 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 bacteria and antibacterial medications, it is also reasonable to talk about cancer and cancer treatment. I truly hope cancer will meet its "penicillin" one day (yes I know this is unlikely).
- dpark 4mo ago
  It seems relevant here because the question was “How will this potentially help me if I get cancer?” and the answer is “Not at all unless you get a particular form of cancer that this applies to”. > 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. Except people don’t ask “what if I get bacteria” the way they ask about cancer. If the story was about a new antibiotic that only affected 20% of common infectious bacteria strains and someone asked “in laypersons terms, how will this help me if I get a bacterial infection”, it would be appropriate to clarify that it only applies to some bacteria.
  - LoganDark 4mo ago
    > Except people don’t ask “what if I get bacteria” the way they ask about cancer. Yeah, but doctors also don't tell people "you have bacteria" or claim "we found a cure for bacteria". The lack of nuance on average is largely due to a lack of nuance from experts. The media treats cancer as one big thing and bacteria and viruses as separate things. Thus the average joe inherits 'treating cancer as one big thing' from the media.
    - jldugger 4mo ago
      Is it? I'm pretty sure oncologists will say "you have stage 2 breast cancer," but I wasn't in the room at the time.
dyauspitr 4mo ago
The golden panacea for this would be a gene editing mechanism that will work in every cell in the body. Once we have something we can do whole hog gene replacement, most human health problems would be solved forever.
- tremon 4mo ago
  For every cell mechanism that's being abused by cancer to fuel its growth, there are other cells in the body for which that mechanism is crucial for their correct functioning. Wholesale editing every cell in the body mostly guarantees that the patient does not die of cancer -- the cure will kill them before the disease does.
  - dyauspitr 4mo ago
    Only cells that have the necessary signature get the edit
    - Hendrikto 4mo ago
      So the exact opposite of what you said initially.
      - dyauspitr 4mo ago
        No, a mechanism that acts on every cell on the body doesn’t mean it changes every cell. The primary problem with gene replacement therapies is they cannot be effectively delivered to every cell. If we can find a way to deliver to every cell than just the ones with the right signature will get the changes.
juleiie 4mo ago
[flagged]
- epistasis 4mo ago
  Are you going to give them cancer first too? This is a horrifying proposal not only on the ethics front but also in the scientific uselessness of it. This is exactly the type of thing that gave the Nazis the bad name they deserve.
  - juleiie 4mo ago
    [flagged]
    - wongarsu 4mo ago
      Until you get to the second order effects. If we want to find a cure for some disease, but we don't have enough people to do experiments on (maybe a lot of eligable prisoners died in previous trials) judges now have an incentive to hand out life sentences to people with that medical condition Even just subconsciously that would have an effect
      - juleiie 4mo ago
        [flagged]
        deleted 4mo ago
        [deleted]
        wongarsu 4mo ago
        That won't create justice, only judges that forever encode current prejudices
        ycombinator_acc 4mo ago
        As opposed to future prejudices? I agree: the trials are not speedy enough. None of us will live long enough to take advantage of the endgame version of this.
basisword 4mo ago
Thanks for the explanation!
inigyou 4mo ago
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?
- epistasis 4mo ago
  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.
- jibal 4mo ago
  This drug targets cells with a KRAS mutation that locks the KRAS switch in the ON state, driving uncontrolled growth. Cells with this mutation are abnormal and predisposed to becoming cancer ... so by definition are not healthy.
throwaway81523 4mo ago
Can we end up with a situation like antimicrobial resistance, where cancer itself evolves to resist these new treatments?
- ulbu 4mo ago
  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.
  - 8note 4mo ago
    the single celled dog might beg to differ. sometimes a cancer can then survive on its own back as a single celled organism
  - throwaway81523 4mo ago
    I've heard that some cancers spread by viruses. Viruses do evolve. No idea if that says anything about cancer evolving.
  - epistasis 4mo ago
    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 https://www.nature.com/articles/s41586-019-1907-7
  - nly 4mo ago
    You might want to read this https://en.wikipedia.org/wiki/HeLa https://en.wikipedia.org/wiki/HeLa
- nicwilson 4mo ago
  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.

siva7 4mo ago

It won't help... mind you this is an article from the economist. There is no such thing as a cancer "master switch", that would equal a disease master switch and that point we have solved biology.

sarchertech 4mo ago
What do you mean “it won’t help”? It most likely will help if you get pancreatic cancer. It might help if you get one of the other types of cancers with this mutation. And it will likely lead to new treatments for some of the worst kinds of cancer.