Every year at AACR meetings there seems to be a new update on how researchers are doing with their work on overcoming resistance in metastatic melanoma. We’ve seen some stunning photos where targeting the BRAF V600E mutation with a specific kinase inhibitor such as vemurafenib (Zelboraf) or dabrafenib (Tafinlar) results in dramatic reduction, and sometimes even complete disappearance of the lesions, only for resistance to set in and the melanoma sadly comes back with a vengeance. Adding a MEK inhibitor such as trametinib (Mekinist) was originally thought to be a rather promising strategy, until it became clear that this only gave a few extra months with exactly the same result.

Over on Pharma Strategy Blog, I’ve written a lot about the fascinating research on various mechanisms of resistance in this disease. They range from specific mutations emerging to activation of COT or MEK and others in response to therapy. There are a number of questions we can ask that need to be addressed:

  • Do we need a better/more potent BRAF inhibitor?
  • Do we need a better/more potent MEK inhibitor?
  • What other combinations and targets can be explored?
  • Is timing and dosing important? (e.g. continuous vs. intermittent dosing)
  • And many others…

AACR 2012 Bill Sellers Picture 300x168 Update on overcoming resistance in metastatic melanomaAt the recent AACR Molecular Targets meeting in Boston I chatted with Dr Bill Sellers, who is the Global Head of Oncology Research at the Novartis Institutes for Biomedical Research (NIBR) and oversees the drug discovery efforts in this space for Novartis.

Yesterday we highlighted NIBR’s work with CDK4/6 inhibition in breast cancer, but this compound may have surprising utility in metastatic melanoma.

Novartis also have several other melanoma agents in their pipeline in the clinic, including a BRAF inhibitor (LGX818), a MEK inhibitor (MEK162) and more recently, an Mdm2 inhibitor (CGM097) in preclinical development.

To read more about the new developments in advanced melanoma, you can sign in or sign up below.

 Update on overcoming resistance in metastatic melanoma

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