Therapeutic approach to treating patients with BRAF-mutant lung cancer: latest evidence and clinical implications

Abstract

Lung adenocarcinoma is known for its high rate of somatic mutations and genomic rearrangements. The identification of epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements that sensitize tumors to specific drugs has changed the therapeutic approach and prognosis in these molecularly-defined subgroups. Several other key genetic alterations have been identified, of which BRAF mutations are found in 4% of non-small cell lung cancer (NSCLC) cases. Targeted drugs against BRAF and downstream MEK were recently approved for the treatment of BRAF-positive melanoma and have entered clinical evaluation in NSCLC. In this review we discuss the latest evidence on the treatment of BRAF-mutated NSCLC, including tumor biology, targeted treatment with BRAF and MEK inhibitors, therapeutic resistance and strategies to overcome resistance.