What links BRAF to the heart function? New insights from the cardiotoxicity of BRAF inhibitors in cancer treatment

Oncotarget. 2015 Nov 3;6(34):35589-601. doi: 10.18632/oncotarget.5853.


The RAS-related signalling cascade has a fundamental role in cell. It activates differentiation and survival. It is particularly important one of its molecules, B-RAF. B-RAF has been a central point for research, especially in melanoma. Indeed, it lacked effective therapeutic weapons since the early years of its study. Molecules targeting B-RAF have been developed. Nowadays, two classes of molecules are approved by FDA. Multi-target molecules, such as Sorafenib and Regorafenib, and selective molecules, such as Vemurafenib and Dabrafenib. Many other molecules are still under investigation. Most of them are studied in phase 1 trials. Clinical studies correlate B-RAF inhibitors and QT prolongation. Though this cardiovascular side effect is not common using these drugs, it must be noticed early and recognize its signals. Indeed, Oncologists and Cardiologists should work in cooperation to prevent lethal events, such as fatal arrhythmias or sudden cardiac death. These events could originate from an uncontrolled QT prolongation.

Keywords: B-RAF; B-RAF inhibitors; cardio-oncology; cardiotoxicity; dabrafenib.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Arrhythmias, Cardiac / chemically induced
  • Arrhythmias, Cardiac / prevention & control*
  • Clinical Trials as Topic
  • Heart / drug effects*
  • Heart / physiology
  • Humans
  • Melanoma / drug therapy*
  • Molecular Targeted Therapy
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Proto-Oncogene Proteins B-raf / metabolism*
  • Signal Transduction / drug effects
  • Skin Neoplasms / drug therapy*


  • Antineoplastic Agents
  • Protein Kinase Inhibitors
  • Proto-Oncogene Proteins B-raf