Activated MEK cooperates with Cdkn2a and Pten loss to promote the development and maintenance of melanoma.

ABSTRACT: The development of targeted inhibitors, vemurafenib and dabrafenib, has led to improved clinical outcome for melanoma patients with BRAF^V600E mutations. Although the initial response to these inhibitors can be dramatic, sometimes causing complete tumor regression, the majority of melanomas eventually become resistant. Mitogen-activated protein kinase kinase (MEK) mutations are found in primary melanomas and frequently reported in BRAF melanomas that develop resistance to targeted therapy; however, melanoma is a molecularly heterogeneous cancer, and which mutations are drivers and which are passengers remains to be determined. In this study, we demonstrate that in BRAF^V600E melanoma cell lines, activating MEK mutations drive resistance and contribute to suboptimal grow

SUBMITTER: Yang H 

PROVIDER: S-EPMC5501768 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature