Review
Version 1
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Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2
Version 1
: Received: 2 September 2023 / Approved: 4 September 2023 / Online: 5 September 2023 (03:53:23 CEST)
A peer-reviewed article of this Preprint also exists.
Chen, W.; Park, J.-I. Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2. Int. J. Mol. Sci. 2023, 24, 14837. Chen, W.; Park, J.-I. Tumor Cell Resistance to the Inhibition of BRAF and MEK1/2. Int. J. Mol. Sci. 2023, 24, 14837.
Abstract
BRAF is one of the most frequently mutated oncogenes, with an overall frequency of about 50%. Targeting BRAF and its effector mitogen-activated protein kinase kinase 1/2 (MEK1/2) is now a key therapeutic strategy for BRAF-mutant tumors, and therapies based on dual BRAF/MEK inhibition showed significant efficacy in a broad spectrum of BRAF tumors. Nonetheless, BRAF/MEK inhibition therapy is not always effective for BRAF tumor suppression, and significant challenges remain to improve its clinical outcomes. First, certain BRAF tumors have an intrinsic ability to rapidly adapt to the presence of BRAF and MEK1/2 inhibitors by bypassing drug effects via rewired signaling, metabolic, and regulatory networks. Second, almost all tumors initially responsive to BRAF and MEK1/2 inhibitors eventually acquire therapy resistance via an additional genetic or epigenetic alteration(s). Overcoming these challenges requires identifying the molecular mechanism underlying tumor cell resistance to BRAF and MEK inhibitors and analyzing their specificity in different BRAF tumors. This review aims to update this information.
Keywords
BRAF; MEK; tumor; drug resistance
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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