Advances in anti-BRAF therapies for lung cancer

Abstract

Non-small cell lung cancer (NSCLC) is one of the most frequent causes of mortality in the western world. v-raf murine sarcoma viral oncogene homolog B (BRAF) is a member of the Raf kinase family and plays a critical role in cellular growth, proliferation, and differentiation through the mitogen-activated protein kinase pathway. The incidence of BRAF mutations in NSCLC is low, accounting for 0-3% of all cases of lung cancer. Given the results obtained in metastatic melanoma, several studies have reported the efficacy of anti-BRAF therapies in NSCLC treatment. In this review, we describe changes in the landscape of BRAF-mutated lung cancer treatment and analyze insights from major clinical trials in the context of future therapeutic prospects.

Keywords: BRAF; Lung cancer; V600.

Fig. 1

Normal functional MAPK/ERK pathway in wild-type (WT) BRAF and its alteration in the presence of BRAF^V600E mutation and the mechanism of action of drugs targeting the mutation. Normal functional MAPK/ERK pathway is activated after extracellular signaling, leading to a response in cell cycle control, proliferation, and cellular migration. The BRAF^V600E mutation induces a self-sustained constant activation of the MAPK/ERK pathway, thereby inhibiting controlled cellular death by apoptosis via indirect regulation of BAD. The BRAF^V600E pathway drastically increases the basal levels of proliferation, consistent with oncogenic development. Therefore, the BRAF^V600E mutation could be targeted for treatment with specific inhibitors, which results in an increase in apoptotic activity