Targeting Oncogenic BRAF: Past, Present, and Future
Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resista...
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doaj-3bbeafb0c2ea4764b46cd9b713f1b1c52020-11-25T00:50:11ZengMDPI AGCancers2072-66942019-08-01118119710.3390/cancers11081197cancers11081197Targeting Oncogenic BRAF: Past, Present, and FutureAubhishek Zaman0Wei Wu1Trever G. Bivona2Department of Medicine, University of California, San Francisco, CA 94143, USADepartment of Medicine, University of California, San Francisco, CA 94143, USADepartment of Medicine, University of California, San Francisco, CA 94143, USAIdentifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies.https://www.mdpi.com/2072-6694/11/8/1197BRAFoncogeneprecision medicinetargeted therapydrug resistance |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Aubhishek Zaman Wei Wu Trever G. Bivona |
spellingShingle |
Aubhishek Zaman Wei Wu Trever G. Bivona Targeting Oncogenic BRAF: Past, Present, and Future Cancers BRAF oncogene precision medicine targeted therapy drug resistance |
author_facet |
Aubhishek Zaman Wei Wu Trever G. Bivona |
author_sort |
Aubhishek Zaman |
title |
Targeting Oncogenic BRAF: Past, Present, and Future |
title_short |
Targeting Oncogenic BRAF: Past, Present, and Future |
title_full |
Targeting Oncogenic BRAF: Past, Present, and Future |
title_fullStr |
Targeting Oncogenic BRAF: Past, Present, and Future |
title_full_unstemmed |
Targeting Oncogenic BRAF: Past, Present, and Future |
title_sort |
targeting oncogenic braf: past, present, and future |
publisher |
MDPI AG |
series |
Cancers |
issn |
2072-6694 |
publishDate |
2019-08-01 |
description |
Identifying recurrent somatic genetic alterations of, and dependency on, the kinase BRAF has enabled a “precision medicine” paradigm to diagnose and treat BRAF-driven tumors. Although targeted kinase inhibitors against BRAF are effective in a subset of mutant BRAF tumors, resistance to the therapy inevitably emerges. In this review, we discuss BRAF biology, both in wild-type and mutant settings. We discuss the predominant BRAF mutations and we outline therapeutic strategies to block mutant BRAF and cancer growth. We highlight common mechanistic themes that underpin different classes of resistance mechanisms against BRAF-targeted therapies and discuss tumor heterogeneity and co-occurring molecular alterations as a potential source of therapy resistance. We outline promising therapy approaches to overcome these barriers to the long-term control of BRAF-driven tumors and emphasize how an extensive understanding of these themes can offer more pre-emptive, improved therapeutic strategies. |
topic |
BRAF oncogene precision medicine targeted therapy drug resistance |
url |
https://www.mdpi.com/2072-6694/11/8/1197 |
work_keys_str_mv |
AT aubhishekzaman targetingoncogenicbrafpastpresentandfuture AT weiwu targetingoncogenicbrafpastpresentandfuture AT trevergbivona targetingoncogenicbrafpastpresentandfuture |
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