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

Abstract

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.

Identification of novel natural drug candidates against BRAF mutated carcinoma; An integrative in-silico structure-based pharmacophore modeling and virtual screening process

“…It has been identified BRAF mutations as the most frequent mutations related to human carcinomas such as thyroid cancer, ovarian cancer, hepatic carcinoma, and hairy cell leukaemia. The most common mutation has been observed at V600E by sequencing ( Yan et al, 2022 ). The discovery against this BRAF mutation target are in some clinical trial phase and currently using the drugs showing the side effects after administration to the patients (A.…”

Application of Selective SMARCA2/4 PROTAC for Mutant Cancer Therapy

“…The table below shows percentage of SMARCA2 or SMARCA4 degradation. Compounds 2 , 5 , 6 , and 11 were screened and their EC 50 values (nM) determined, and all resulted in EC 50 values that were lower than 250 nM. …”

Application of Rapidly Accelerating Fibrosarcoma Protein Degraders in Drug Discovery

“…The table below shows degradation and characterization of exemplary bifunctional compounds: DC 50 V600E (nM), where A ≤ 5, 5 < B ≤ 50; DC 50 G446V (nM), where A ≤ 1; 1 < B ≤ 10; and D Max (%), where A ≥ 70, 35 < B < 70. …”