Epigenetic Mechanisms of Escape from BRAF Oncogene Dependency

About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAP...

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Published inCancers Vol. 11; no. 10; p. 1480
Main Authors Khaliq, Mehwish, Fallahi-Sichani, Mohammad
Format Journal Article
LanguageEnglish
Published Basel MDPI AG 01.10.2019
MDPI
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ISSN2072-6694
2072-6694
DOI10.3390/cancers11101480

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Summary:About eight percent of all human tumors (including 50% of melanomas) carry gain-of-function mutations in the BRAF oncogene. Mutated BRAF and subsequent hyperactivation of the MAPK signaling pathway has motivated the use of MAPK-targeted therapies for these tumors. Despite great promise, however, MAPK-targeted therapies in BRAF-mutant tumors are limited by the emergence of drug resistance. Mechanisms of resistance include genetic, non-genetic and epigenetic alterations. Epigenetic plasticity, often modulated by histone-modifying enzymes and gene regulation, can influence a tumor cell’s BRAF dependency and therefore, response to therapy. In this review, focusing primarily on class 1 BRAF-mutant cells, we will highlight recent work on the contribution of epigenetic mechanisms to inter- and intratumor cell heterogeneity in MAPK-targeted therapy response.
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ISSN:2072-6694
2072-6694
DOI:10.3390/cancers11101480