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- October 11, 2011 at 7:29 pm


Melanoma pathways and targeted therapeutics. Several investigational agents designed to inhibit cell-autonomous melanoma pathways or augment antimelanoma immune mechanisms have entered clinical development. Proteins that have been targeted in melanoma clinical trials are indicated (red bars and bold arrow). The MAP kinase pathway (bottom left) has been targeted by RAF and MEK inhibitors, the PI3 kinase/ AKT pathway (bottom right) by TOR inhibitors, and the cell cycle by CDK inhibitors (bottom middle). Drugs inhibiting the Hsp90 chaperone protein may lead to degradation of several activated oncogenes (see text for details). The Bcl-2 antiapoptotic oncoprotein has been targeted by an antisense agent. Aside from IFN-α and IL-2, recent attempts to enhance melanoma immunotherapy include toll-like receptor agonists (top left) and CTLA-4 antibody blockade (top middle). These are predicted to generate a more effective T-cell-mediated immunotoxicity to melanoma cells. Strategies to interdict RTK such as c-kit may prove fruitful in the future against defined melanoma subtypes.
Best regards,
Jimmy B
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