The broad-spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF-mutant melanoma cells in combination with other signaling pathway inhibitors.

ABSTRACT: BRAF inhibitors have revolutionized treatment of mutant BRAF metastatic melanomas. However, resistance develops rapidly following BRAF inhibitor treatment. We have found that BRAF-mutant melanoma cell lines are more sensitive than wild-type BRAF cells to the small molecule tyrosine kinase inhibitor dovitinib. Sensitivity is associated with inhibition of a series of known dovitinib targets. Dovitinib in combination with several agents inhibits growth more effectively than either agent alone. These combinations inhibit BRAF-mutant melanoma and colorectal carcinoma cell lines, including cell lines with intrinsic or selected BRAF inhibitor resistance. Hence, combinations of dovitinib with second agents are potentially effective therapies for BRAF-mutant melanomas, regardless of their sensitivity to BRAF inhibitors.

SUBMITTER: Langdon CG 

PROVIDER: S-EPMC5215495 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature