Dissecting therapeutic resistance to RAF inhibition in melanoma by tumor genomic profiling.

ABSTRACT: A detailed understanding of the mechanisms by which tumors acquire resistance to targeted anticancer agents should speed the development of treatment strategies with lasting clinical efficacy. RAF inhibition in BRAF-mutant melanoma exemplifies the promise and challenge of many targeted drugs; although response rates are high, resistance invariably develops. Here, we articulate overarching principles of resistance to kinase inhibitors, as well as a translational approach to characterize resistance in the clinical setting through tumor mutation profiling. As a proof of principle, we performed targeted, massively parallel sequencing of 138 cancer genes in a tumor obtained from a patient with melanoma who developed resistance to PLX4032 after an initial dramatic response. The resulting profile

SUBMITTER: Wagle N 

PROVIDER: S-EPMC3157968 | biostudies-literature | 2011 Aug

REPOSITORIES: biostudies-literature