Work

Preclinical efficacy of a RAF inhibitor that evades paradoxical MAPK pathway activation in protein kinase BRAF -mutant lung cancer

Year: 2016

Type: article

Abstract: Significance Oncogenic mutations in the BRAF protein kinase occur in a large number of patients with lung cancer, the number one cause of cancer mortality worldwide. Despite the relatively high frequency (2–7%) of various oncogenic BRAF alleles in human lung adenocarcinoma (LA), the biological and clinical relevance of these mutations and the optimal therapeutic strategy to improve outcomes remains poorly defined. We report the preclinical efficacy of a next-generation BRAF kinase inhibitor across a spectrum of clinically relevant BRAF -mutant nonsmall cell lung cancer (NSCLC) models. Our results provide biological insight into the regulation of BRAF oncogene dependence and identify strategies to improve outcomes in patients with BRAF -mutant lung cancer.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.1610456113