4 ms·

> There is absolutely no reason that approved anti-cancer drugs in one cancer type and stage should be limited to just those cases. Can you expand on that?

chrisamiller 11y ago
Mutations in the BRAF gene, to name one druggable example, are a cause of many different types of cancer - melanoma, some breast, small-cell lung cancer, etc. Under the current paradigm, each type of cancer is treated as a different disease and requires a different clinical trial. This is bad. What should happen (and is beginning to happen, with "basket trials") is that cancers are grouped by their genetic profile, instead of their tissue of origin. The BRAF V600E mutation is targetable with Vemurafenib, and so that drug should be used regardless of whether you have breast cancer or lung cancer.
- niels_olson 11y ago
  Perhaps, but it is also true that these targeted therapies have different success rates among different cancers. Vemurafenib, famously approved for melanoma, hasn't been as successful in papillary thyroid.
- OopsCriticality 11y ago
  Certainly it makes sense to consider genetic profile in treatment, but doesn't the statement "that drug should be used regardless of whether you have breast cancer or lung cancer" ignore the local tumor microenvironment and possible differences in drug resistance expression between cell types, i.e., isn't reducing cancer down to genetic profile alone potentially as problematic as reducing cancer down to its tissue of origin?
  - chrisamiller 11y ago
    Your points are right on - I oversimplified while trying to explain the concept.
- dnautics 11y ago
  This isn't really that much of an issue because oncologists are not always idiots and can prescribe drugs off-label, with cause. Identifying a braf mutant in a disparate cancer type would probably qualify.
  - sjg007 11y ago
    It is a huge issue. They risk FDA censure and it usually requires IRB approval as well. It will change with precision medicine but it won't change fast enough. People really need to read DeVita's book. All of my comments are taken from his arguments. DeVita was the chief of the NCI for 30 years.

chrisamiller 11y ago

Mutations in the BRAF gene, to name one druggable example, are a cause of many different types of cancer - melanoma, some breast, small-cell lung cancer, etc. Under the current paradigm, each type of cancer is treated as a different disease and requires a different clinical trial. This is bad. What should happen (and is beginning to happen, with "basket trials") is that cancers are grouped by their genetic profile, instead of their tissue of origin. The BRAF V600E mutation is targetable with Vemurafenib, and so that drug should be used regardless of whether you have breast cancer or lung cancer.

niels_olson 11y ago
Perhaps, but it is also true that these targeted therapies have different success rates among different cancers. Vemurafenib, famously approved for melanoma, hasn't been as successful in papillary thyroid.
OopsCriticality 11y ago
Certainly it makes sense to consider genetic profile in treatment, but doesn't the statement "that drug should be used regardless of whether you have breast cancer or lung cancer" ignore the local tumor microenvironment and possible differences in drug resistance expression between cell types, i.e., isn't reducing cancer down to genetic profile alone potentially as problematic as reducing cancer down to its tissue of origin?
- chrisamiller 11y ago
  Your points are right on - I oversimplified while trying to explain the concept.
dnautics 11y ago
This isn't really that much of an issue because oncologists are not always idiots and can prescribe drugs off-label, with cause. Identifying a braf mutant in a disparate cancer type would probably qualify.
- sjg007 11y ago
  It is a huge issue. They risk FDA censure and it usually requires IRB approval as well. It will change with precision medicine but it won't change fast enough. People really need to read DeVita's book. All of my comments are taken from his arguments. DeVita was the chief of the NCI for 30 years.