4.6 Review

BRAF-Mutated Non-Small Cell Lung Cancer: Current Treatment Status and Future Perspective

Journal

FRONTIERS IN ONCOLOGY
Volume 12, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fonc.2022.863043

Keywords

BRAF; NSCLC; targeted therapy; immune checkpoint inhibitors; tyrosine kinase inhibitors

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Funding

  1. joint construction project of Henan Province and Ministry [LHGJ20190013]

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This review summarizes the characteristics and challenges of BRAF mutations in NSCLC, as well as the treatment strategies and resistance mechanisms of BRAF-targeted therapy.
V-Raf murine sarcoma viral oncogene homolog B (BRAF) kinase, which was encoded by BRAF gene, plays critical roles in cell signaling, growth, and survival. Mutations in BRAF gene will lead to cancer development and progression. In non-small cell lung cancer (NSCLC), BRAF mutations commonly occur in never-smokers, women, and aggressive histological types and accounts for 1%-2% of adenocarcinoma. Traditional chemotherapy presents limited efficacy in BRAF-mutated NSCLC patients. However, the advent of targeted therapy and immune checkpoint inhibitors (ICIs) have greatly altered the treatment pattern of NSCLC. However, ICI monotherapy presents limited activity in BRAF-mutated patients. Hence, the current standard treatment of choice for advanced NSCLC with BRAF mutations are BRAF-targeted therapy. However, intrinsic or extrinsic mechanisms of resistance to BRAF-directed tyrosine kinase inhibitors (TKIs) can emerge in patients. Hence, there are still some problems facing us regarding BRAF-mutated NSCLC. In this review, we summarized the BRAF mutation types, the diagnostic challenges that BRAF mutations present, the strategies to treatment for BRAF-mutated NSCLC, and resistance mechanisms of BRAF-targeted therapy.

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