Over half of patients with melanoma exhibit v‑Raf murine sarcoma viral oncogene homolog B (BRAF) mutations, which drive hyperactivation of the MAPK pathway and confer high proliferative potential. To target this oncogenic mutation, BRAF inhibitors, as well as MEK inhibitors (targeting the downstream effector of BRAF), have been approved for melanoma therapy. Although these inhibitors initially decrease the tumor burden, nearly all patients eventually develop drug resistance, leading to aggressive disease relapse at both the primary and metastatic sites. Understanding the mechanisms underlying tumor escape from drug lethality is crucial for the development of strategies against melanoma. The present study aimed to summarize the discovery, development and clinical evolution of the BRAF and MEK inhibitors approved for the treatment of melanoma, their notable efficacy in suppressing aggressive melanoma progression and the underlying mechanisms of acquired resistance.
Zhang et al. (Thu,) studied this question.