Oncotarget

Research Perspectives:

Targeting the multifaceted BRAF in cancer: New directions

Eamon Toye, Alexander Chehrazi-Raffle, Justin Hwang _ and Emmanuel S. Antonarakis _

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Oncotarget. 2024; 15:486-492. https://doi.org/10.18632/oncotarget.28612

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Abstract

Eamon Toye1,2,3, Alexander Chehrazi-Raffle4, Justin Hwang1,2 and Emmanuel S. Antonarakis1,2

1 Masonic Cancer Center, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA

2 Department of Medicine, University of Minnesota-Twin Cities, Minneapolis, MN 55455, USA

3 Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19146, USA

4 City of Hope Comprehensive Cancer Center, Duarte, CA 91010, USA

Correspondence to:

Emmanuel S. Antonarakis, email: [email protected]
Justin Hwang, email: [email protected]

Keywords: BRAF; MAPK; pan-cancer; precision oncology; genomics

Received: July 01, 2024     Accepted: July 07, 2024     Published: July 16, 2024

Copyright: © 2024 Toye et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Activating mutations in the mitogen-activated protein kinase (MAPK) pathway represent driver alterations governing tumorigenesis, metastasis, and therapy resistance. MAPK activation predominantly occurs through genomic alterations in RAS and BRAF. BRAF is an effector kinase that functions downstream of RAS and propagates this oncogenic activity through MEK and ERK. Across cancers, BRAF alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I BRAF alterations (p.V600 hotspot mutations) in tumors such as melanomas, thyroid cancers, and colorectal cancers. However, numerous non-Class I BRAF inhibitors are also in development and have been explored in some cancers. Here we discuss the diverse forms of BRAF alterations found in human cancers and the strategies to inhibit them in patients harboring cancers of distinct origins.


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