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Hendrickson AW, Meng XW, Kaufmann SH: Anticancer therapy: boosting the bang of Bim. J Clin Invest. 2008 Nov;118(11):3582-4. Epub 2008 Oct 23.
Even though activating mutations of B-Raf, a kinase atop the MAPK signaling cascade, reportedly sensitize tumor cells to MEK inhibitors, Raf and MEK inhibitors have exhibited limited clinical activity. In this issue of the JCI, Cragg et al. report that MEK inhibition upregulates the proapoptotic Bcl-2 family member Bim but induces little regression of human melanoma xenografts in mice unless the Bcl-2 antagonist ABT-737 is added (see the related article beginning on page 3651). These findings illustrate the potential benefit of simultaneously inhibiting oncogenic kinases and inhibiting Bcl-2 action in solid tumors. |
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