Rho-mediated signaling promotes BRAF inhibitor resistance in de-differentiated melanoma cells.

ABSTRACT: Over half of cutaneous melanoma tumors have BRAF^V600E/K mutations. Acquired resistance to BRAF inhibitors (BRAFi) remains a major hurdle in attaining durable therapeutic responses. In this study we demonstrate that ~50-60% of melanoma cell lines with vemurafenib resistance acquired in vitro show activation of RhoA family GTPases. In BRAFi-resistant melanoma cell lines and tumors, activation of RhoA is correlated with decreased expression of melanocyte lineage genes. Using a machine learning approach, we built gene expression-based models to predict drug sensitivity for 265 common anticancer compounds. We then projected these signatures onto the collection of TCGA cutaneous melanoma and found that poorly differentiated tumors were predicted to have increased sensitivity to multip

SUBMITTER: Misek SA 

PROVIDER: S-EPMC7024013 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature