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The broad‐spectrum receptor tyrosine kinase inhibitor dovitinib suppresses growth of BRAF ‐mutant melanoma cells in combination with other signaling pathway inhibitors
Author(s) -
Langdon Casey G.,
Held Matthew A.,
Platt James T.,
Meeth Katrina,
Iyidogan Pinar,
Mamillapalli Ramanaiah,
Koo Andrew B.,
Klein Michael,
Liu Zongzhi,
Bosenberg Marcus W.,
Stern David F.
Publication year - 2015
Publication title -
pigment cell and melanoma research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.618
H-Index - 105
eISSN - 1755-148X
pISSN - 1755-1471
DOI - 10.1111/pcmr.12376
Subject(s) - cancer research , mutant , melanoma , tyrosine kinase inhibitor , tyrosine kinase , mek inhibitor , cell culture , receptor tyrosine kinase , growth inhibition , kinase , biology , receptor , medicine , mapk/erk pathway , cancer , microbiology and biotechnology , biochemistry , genetics , gene
Summary 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.