3 ms·

Depends on what you mean by "fail hard," I suspect. Sure, cancer cells can gain or lose mutations, but if we target a mutation important for cancer development

Depends on what you mean by "fail hard," I suspect. Sure, cancer cells can gain or lose mutations, but if we target a mutation important for cancer development only a fraction of the target cancer will survive the treatment. We might achieve nice-to-have results like reduction in tumor size and increased patient life expectancy, or a "cure" in lucky patients with less agile cancers, which would put this radical new intervention in line with most standard cancer treatments. As a total cure for cancer it will "fail," but then, so have all the breakthrough cancer treatments that have collectively shattered the mortality rates of cancer patients. (You mention you're involved in cancer research, so you presumably know all this already- I'm wondering if there's a more nuanced reason for this pessimism.) The best theory I've heard so far as to how we'll "cure cancer" altogether is that we'll simply develop a big enough armory of anticancer treatments that no individual cancer case could evolve fast enough to beat them all. Unlike bacteria or viruses, cancers evolve on their own and when they're done their evolutionary innovations die with them. Our technology lives on, though, so we can hope to eventually just totally outclass their capabilities. If CRISPR gives us another source of these partial treatments, we're just that much closer to that level.

astazangasta 10y ago
This method is not targeting mutations important for cancer, this is targeting "passenger" somatic mutations. You can't use this mechanism to target important mutations because only a minority of patients are going to be able to present an oncogenic mutation (e.g. BRAF V600E) as an antigen (because of differing HLA types). In those rare cases perhaps this therapy might succeed, although the tumor probably still has ways of evading (downregulating the offending HLA for example). As for the "kitchen sink" approach, so far none of the methods we've developed are free from side effects. Cancer patients are often on the edge of death; each successive therapy will probably do more damage to them. As it is most people fail on current immunotherapies because of autoimmune reactions. So relentless application of therapies is not necessarily going to work, though of course having more weapons in our arsenal is great.
- danieltillett 10y ago
  I was under the impression that the major reason for the failure of current immunotherapy treatments is due to non-response, not excessive autoimmunity.
  - astazangasta 10y ago
    Sorry, you're absolutely right. I should say 'many', not 'most', my comment was hasty. It varies with the therapy and only a minority of patients fail because of adverse immune events, and the drug matters - ipilimumab (anti-CLTA4) had 10-15% severe immune-related adverse events, whereas anti-PD1 is much better tolerated (probably because the immune checkpoint is later). Combination therapies (ipi + nivo) have much higher adverse event rates, unsurprisingly.
deleted 10y ago
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astazangasta 10y ago

This method is not targeting mutations important for cancer, this is targeting "passenger" somatic mutations. You can't use this mechanism to target important mutations because only a minority of patients are going to be able to present an oncogenic mutation (e.g. BRAF V600E) as an antigen (because of differing HLA types). In those rare cases perhaps this therapy might succeed, although the tumor probably still has ways of evading (downregulating the offending HLA for example). As for the "kitchen sink" approach, so far none of the methods we've developed are free from side effects. Cancer patients are often on the edge of death; each successive therapy will probably do more damage to them. As it is most people fail on current immunotherapies because of autoimmune reactions. So relentless application of therapies is not necessarily going to work, though of course having more weapons in our arsenal is great.

danieltillett 10y ago
I was under the impression that the major reason for the failure of current immunotherapy treatments is due to non-response, not excessive autoimmunity.
- astazangasta 10y ago
  Sorry, you're absolutely right. I should say 'many', not 'most', my comment was hasty. It varies with the therapy and only a minority of patients fail because of adverse immune events, and the drug matters - ipilimumab (anti-CLTA4) had 10-15% severe immune-related adverse events, whereas anti-PD1 is much better tolerated (probably because the immune checkpoint is later). Combination therapies (ipi + nivo) have much higher adverse event rates, unsurprisingly.

deleted 10y ago

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