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Review
. 2022 Nov;23(11):1503-1521.
doi: 10.1007/s11864-022-01006-7. Epub 2022 Oct 1.

BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies

Jingqin Zhong  1 , Wangjun Yan  1 , Chunmeng Wang  1 , Wanlin Liu  1 , Xinyi Lin  1 , Zijian Zou  1 , Wei Sun  2 , Yong Chen  3
Affiliations
Review

BRAF Inhibitor Resistance in Melanoma: Mechanisms and Alternative Therapeutic Strategies

Jingqin Zhong et al. Curr Treat Options Oncol. 2022 Nov.

Erratum in

Abstract

Melanoma is caused by a variety of somatic mutations, and among these mutations, BRAF mutation occurs most frequently and has routinely been evaluated as a critical diagnostic biomarker in clinical practice. The introduction of targeted agents for BRAF-mutant melanoma has significantly improved overall survival in a large proportion of patients. However, there is BRAF inhibitor resistance in most patients, and its mechanisms are complicated and need further clarification. Additionally, treatment approaches to overcome resistance have evolved rapidly, shifting from monotherapy to multimodality treatment, which has dramatically improved patient outcomes in clinical trials and practice. This review highlights the mechanisms of BRAF inhibitor resistance in melanoma and discusses the current state of its therapeutic approaches that can be further explored in clinical practice.

Keywords: BRAF inhibitor; BRAF mutation; Combination therapy; Melanoma; Resistance mechanism; Targeted therapy.

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Conflict of interest statement

This work was supported by Shanghai Science and Technology Development Funds (19411951700), the Lingang Laboratory (Grant No. LG-QS-202205-11), and the national natural science foundation of China (81802636).

JZ wrote and edited this manuscript and created tables and figure. JZ, ZZ, WS, WY, CW, WL, XL, and YC reviewed and revised the manuscript. WS and YC provided direction and guidance throughout the preparation of the manuscript. All authors read and approved the final manuscript.

Figures

Fig. 1
Fig. 1
The genetic mechanisms of BRAF inhibitor resistance.
Fig. 2
Fig. 2
The role of tumor microenvironment in BRAF inhibitor resistance.
See this image and copyright information in PMC

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