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 in | Cancers Vol. 11; no. 10; p. 1480 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
Basel
MDPI AG
01.10.2019
MDPI |
Subjects | |
Online Access | Get full text |
ISSN | 2072-6694 2072-6694 |
DOI | 10.3390/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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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 ObjectType-Review-3 content type line 23 |
ISSN: | 2072-6694 2072-6694 |
DOI: | 10.3390/cancers11101480 |