Sorafenib-induced cardiovascular toxicity: A cause for concern

Area of Science:

• Cardiovascular Pharmacology
• Oncology
• Molecular Toxicology

Background:

• Sorafenib is a multi-target tyrosine kinase inhibitor used for treating hepatocellular carcinoma, renal cell carcinoma, and thyroid cancer.
• While effective in prolonging survival, sorafenib causes significant cardiovascular toxicity, impacting patient quality of life.
• There is a critical need for effective prevention and treatment strategies for sorafenib-induced cardiovascular complications.

Purpose of the Study:

• To review the incidence and clinical manifestations of sorafenib-induced cardiovascular toxicity.
• To summarize current research on the complex mechanisms underlying this toxicity.
• To explore potential protective strategies against sorafenib's adverse cardiovascular effects.

Main Methods:

• Literature review of clinical studies and preclinical research.
• Synthesis of data on sorafenib's cardiovascular adverse events.
• Analysis of proposed molecular mechanisms including ferroptosis, necroptosis, and ER stress.

Main Results:

• Sorafenib is associated with hypertension, thromboembolism, and heart failure in patients.
• Mechanisms involve ferroptosis, necroptosis, autophagy, mitochondrial damage, and endoplasmic reticulum stress.
• Various agents show protective effects against sorafenib-induced cardiotoxicity in preclinical studies.

Conclusions:

• Sorafenib-induced cardiovascular toxicity presents with diverse clinical issues like hypertension and heart failure.
• Multiple cellular pathways contribute to sorafenib's cardiotoxicity, requiring further elucidation.
• This review provides a foundation for developing targeted therapies to mitigate sorafenib's cardiovascular adverse effects.