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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Risk Stratification, Screening and Treatment of BRAF/MEK Inhibitors-Associated Cardiotoxicity
Isabelle Senechal1,2, Maria Sol Andres3, Jieli Tong3
1Cardio-Oncology Service, Royal Brompton Hospital, Guy's and St. Thomas' NHS Foundation Trust, London, UK. isabelle.senechal-dumais.1@ulaval.ca.
Purpose Of Review:
In this review article we describe the cardiovascular adverse events associated with BRAF and MEK inhibitors as well as their pathophysiologic mechanisms and provide up to date guidance for risk stratified surveillance of patients on treatment and the optimal management of emergent cardiotoxicities.
Recent Findings:
Combination BRAF/MEK inhibition has become an established standard treatment option for patients with a wide variety of BRAF mutant haematological and solid organ cancers, its use is most commonly associated with stage three and metastatic melanoma. The introduction of these targeted drugs has significantly improved the prognosis of previously treatment resistant cancers. It is increasingly recognised that these drugs have a number of cardiovascular toxicities including left ventricular systolic dysfunction, hypertension and QTc interval prolongation. Whilst cardiotoxicity is largely reversible and manageable with medical therapy, it does limit the effective use of these highly active agents.
Insights
BRAF and MEK inhibitors improve cancer prognosis but can cause cardiovascular adverse events like left ventricular dysfunction and hypertension. Early surveillance and management are key for patient safety and effective treatment.
Area of Science:
- Oncology
- Cardiology
- Pharmacology
Background:
- BRAF and MEK inhibitors are standard treatments for BRAF-mutant cancers, notably melanoma.
- These targeted therapies have significantly improved outcomes for previously intractable cancers.
Purpose of the Study:
- To review cardiovascular adverse events associated with BRAF and MEK inhibitors.
- To describe their pathophysiologic mechanisms.
- To provide guidance on surveillance and management of cardiotoxicity.
Main Methods:
- Literature review of cardiovascular adverse events and mechanisms.
- Synthesis of current evidence for risk stratification and management.
Main Results:
- BRAF/MEK inhibitors are linked to cardiotoxicities including left ventricular systolic dysfunction, hypertension, and QTc prolongation.
- These toxicities are largely reversible and manageable with medical therapy.
- Cardiotoxicity can limit the efficacy of these important anti-cancer agents.
Conclusions:
- Cardiovascular surveillance is crucial for patients receiving BRAF and MEK inhibitors.
- Prompt recognition and management of cardiotoxicity are essential for optimal patient outcomes.
- Further research into mitigating cardiotoxicity is warranted.
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