Toxicities from BRAF and MEK Inhibitors: Strategies to Maximize Therapeutic Success

Curr Oncol Rep. 2024 Aug;26(8):934-944. doi: 10.1007/s11912-024-01544-3. Epub 2024 Jun 8.

Abstract

Purpose of review: This report highlights several of the recent therapeutic advancements in the treatment of BRAF-mutant tumors, discusses the most common adverse events observed with BRAF-targeted agents, and suggests strategies to manage and mitigate treatment-related toxicities.

Recent findings: BRAF and MEK inhibitors represent a significant advancement in the treatment of BRAF-mutated malignancies with data across tumor types demonstrating the anti-tumor efficacy of dual MAPK inhibition. Although these agents have a reasonable toxicity profile, variable side effects across organ systems can develop. The discovery of activating BRAF mutations and subsequent development of BRAF and MEK inhibitors has transformed the treatment algorithms of BRAF-mutant malignancies. With increased application of these targeted regimens, identification and prompt management of their unique adverse events are crucial.

Keywords: BRAF inhibition; BRAF mutation; MEK inhibition; Melanoma; NSCLC; Toxicity.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Mitogen-Activated Protein Kinase Kinases / antagonists & inhibitors
  • Molecular Targeted Therapy / adverse effects
  • Mutation
  • Neoplasms* / drug therapy
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Proto-Oncogene Proteins B-raf* / antagonists & inhibitors
  • Proto-Oncogene Proteins B-raf* / genetics

Substances

  • Proto-Oncogene Proteins B-raf
  • Protein Kinase Inhibitors
  • BRAF protein, human
  • Antineoplastic Agents
  • Mitogen-Activated Protein Kinase Kinases