4 ms·

As is often the case, the title is hyperbolic. The discovery applies to 20% of tumors, and "one of cancer's significant defenses" or "a key weakness of cancer"

by gcanyon 4mo ago

As is often the case, the title is hyperbolic. The discovery applies to 20% of tumors, and "one of cancer's significant defenses" or "a key weakness of cancer" would be more accurate. That said, I'll happily take "we discovered a key weakness in 20% of cancers," please and thank you.

basisword 4mo ago
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.)
- 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.
inglor_cz 4mo ago
Aren't those 20 per cent of tumors more concentrated on the "intractable" side? If so, then the hyperbole is forgivable.
- cschmidt 4mo ago
  It does seem like those 20% are exactly on the nasty side. So even more impressive.
  - DataDaoDe 4mo ago
    I'm no expert, and don't know if it applies in this case, but for a cancer I had (lymphoma) I was told that aggressive can often be easier to treat or "cure" (as defined by survival rates, etc.) since it also can often be hit more brutally by the treatments. Anyway, since many in my family have died from this horrible cancer, its fantastic news to hear of any improvements there.
    - jibal 4mo ago
      Sorry, it does not apply ... this drug inhibits (for the first time) the KRAS mutation (previously considered "undruggable") that is the primary cause of 90% of pancreatic cancers and 50% of colon cancers.
      - DataDaoDe 4mo ago
        No reason to be sorry, that sounds like this is even better news then :)
        jibal 4mo ago
        I just meant that this doesn't apply to lymphoma, which is not caused by KRAS.
    - inglor_cz 4mo ago
      Lymphoma is a bit of an outlier. In the case of lymphoma, more aggressive types indeed respond better to treatment, and given that we are now fairly good at treating lymphoma, that translates to good outcomes. That is not true for most cancers, though.
mrcwinn 4mo ago
Only on HN can you get content like this. What a community.
- monster_truck 4mo ago
  You should be thankful that they're posting about a real drug that is in human trials and yet another "in mice" pipedream
asveikau 4mo ago
20% is still a huge number. (Your comment also acknowledges this of course. That just popped out at me.)
jibal 4mo ago
Not hyperbolic, just incomplete ... this drug inhibits the KRAS mutation that is the "master switch" for 90% of pancreatic cancers and 50% of colon cancers. KRAS was considered "undruggable" so this is a huge breakthrough which is why oncologists gave a standing ovation for nearly a minute in the middle of a talk, with some of them in tears.

by gcanyon 4mo ago

basisword 4mo ago

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.)
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.

inglor_cz 4mo ago

Aren't those 20 per cent of tumors more concentrated on the "intractable" side? If so, then the hyperbole is forgivable.

cschmidt 4mo ago
It does seem like those 20% are exactly on the nasty side. So even more impressive.
- DataDaoDe 4mo ago
  I'm no expert, and don't know if it applies in this case, but for a cancer I had (lymphoma) I was told that aggressive can often be easier to treat or "cure" (as defined by survival rates, etc.) since it also can often be hit more brutally by the treatments. Anyway, since many in my family have died from this horrible cancer, its fantastic news to hear of any improvements there.
  - jibal 4mo ago
    Sorry, it does not apply ... this drug inhibits (for the first time) the KRAS mutation (previously considered "undruggable") that is the primary cause of 90% of pancreatic cancers and 50% of colon cancers.
    - DataDaoDe 4mo ago
      No reason to be sorry, that sounds like this is even better news then :)
      - jibal 4mo ago
        I just meant that this doesn't apply to lymphoma, which is not caused by KRAS.
  - inglor_cz 4mo ago
    Lymphoma is a bit of an outlier. In the case of lymphoma, more aggressive types indeed respond better to treatment, and given that we are now fairly good at treating lymphoma, that translates to good outcomes. That is not true for most cancers, though.

mrcwinn 4mo ago

Only on HN can you get content like this. What a community.

monster_truck 4mo ago
You should be thankful that they're posting about a real drug that is in human trials and yet another "in mice" pipedream

asveikau 4mo ago

20% is still a huge number. (Your comment also acknowledges this of course. That just popped out at me.)

jibal 4mo ago

Not hyperbolic, just incomplete ... this drug inhibits the KRAS mutation that is the "master switch" for 90% of pancreatic cancers and 50% of colon cancers. KRAS was considered "undruggable" so this is a huge breakthrough which is why oncologists gave a standing ovation for nearly a minute in the middle of a talk, with some of them in tears.