Targeting the multifaceted BRAF in cancer: New directions

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 and . BRAF is an effector kinase that functions downstream of and...

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Bibliographic Details
Published in:Oncotarget 2024-07, Vol.15 (1), p.486-492
Main Authors: Toye, Eamon, Chehrazi-Raffle, Alexander, Hwang, Justin, Antonarakis, Emmanuel S
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Humans
MAP Kinase Signaling System - genetics
Molecular Targeted Therapy
Mutation
Neoplasms - drug therapy
Neoplasms - genetics
Neoplasms - metabolism
Neoplasms - pathology
Protein Kinase Inhibitors - pharmacology
Protein Kinase Inhibitors - therapeutic use
Proto-Oncogene Proteins B-raf - antagonists & inhibitors
Proto-Oncogene Proteins B-raf - genetics
Proto-Oncogene Proteins B-raf - metabolism
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Summary: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 and . BRAF is an effector kinase that functions downstream of and propagates this oncogenic activity through MEK and ERK. Across cancers, alterations include gain-of-function mutations, copy-number alterations, and structural rearrangements. In cancer patients, BRAF-targeting precision therapeutics are effective against Class I 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 alterations found in human cancers and the strategies to inhibit them in patients harboring cancers of distinct origins.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.28612