Kinome Profiling to Predict Sensitivity to MAPK Inhibition in Melanoma and to Provide New Insights into Intrinsic and Acquired Mechanism of Resistance.

ABSTRACT: Mitogen-activated protein kinase (MAPK) inhibition with the combination of BRAF (Rapidly Accelerated Fibrosarcoma) and MEK (Mitogen-activated protein kinase kinase) inhibitors has become the standard of first-line therapy of metastatic melanoma harbouring BRAF V600 mutations. However, about half of the patients present with primary resistance while the remaining develop secondary resistance under prolonged treatment. Thus, there is a need for predictive biomarkers for sensitivity and/or resistance to further refine the patient population likely to benefit from MAPK inhibitors. In this study, we explored a top-down approach using a multiplex kinase assay, first, to discover a kinome signature predicting sensitivity, intrinsic and acquired resistance to MAPK inhibitors in melanoma, and secon

SUBMITTER: Krayem M 

PROVIDER: S-EPMC7072684 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature