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Exelixis, Inc. Message Board

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  • dr.vinmantoo dr.vinmantoo Feb 24, 2012 11:58 AM Flag

    Dual Inhibition of MET and VEGF Signaling With Cabozantinib Blocks Tumor Invasiveness and Metastasis

    Pre-clinical studies are nice but excellent results in mice often don't translate into excellent results in humans. Nice to read, but yawn is the correct response.

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    • $$$$$

      Not to overplay the significance of these preclinical results, I find it interesting that CABO's unique therapeutic duality is being compared to the likes of approved therapies Sunitinib and Crizotinib in combination w/ known cMET inhibitors. This may provide some early stage indication that a dual inhibitor is somewhat more than the sum of it's components. Particularly if the following 3 statements from the "Marketwatch" article do indeed transfer from preclinical to clinical models.

      Almost seems as if they're trying to replicate CABO results with other known and/or previously approved therapies in combination.

      That being said, the statement regarding comparative survival provides a bit of intrigue,eh?

      "-- Cabozantinib reduced tumor invasiveness compared with VEGF inhibition alone, through a mechanism consistent with MET inhibition.

      -- Liver metastases were completely absent in animals treated with cabozantinib.

      -- Overall survival was longest in cabozantinib-treated animals. All animals treated with cabozantinib survived until the end of the study, whereas most or all animals in all other treatment groups did not survive until the end of the study."

      GLTA

    • $$$$$$$$

      I'm always missing something.

      I looked back just a little ways...
      ..and found this UCSF study dated mid-2011, regarding pancreatic islet cancer, co-authored by Don McDonald, MD. The same D.McDonald, MD that recently published on interactivity & synergy of response with VEGF & c-MET co-inhibition.

      http://cancerres.aacrjournals.org/content/early/2011/05/31/0008-5472.CAN-10-2527.abstract


      It may only be my hunch, but I feel these are the important MOA studies that will determine CABO's overall clinical prospect, and hence it's market value. I am coming to the conclusion that CABO's most unique characteristic seems to be it's continually repetitive ability to display broad preclinical response that actually does statistically translate to broad clinical benefit. How rare a bird is that? We're developing some great data. Keep yer flight harness at the ready.

      I see this slow-motion walkdown as a manipulation.
      GLTA

    • The market may be yawning but scientists and oncology doctors seem to be pretty excited. I think it's likely that the market will eventually catch up with the science.

      Meanwhile, mice,rats and rodents of all kind(not to mention cockroaches), all over the world, are rejoicing.LOL

 
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