Mechanisms and Therapeutic Strategies for VEGFR Inhibitor-Induced Cardiotoxicity and Hepatotoxicity in Cancer Therapy.

Authors

Yajie Peng, Xinyi Chao, Qiubin Song, Zining Li, Shixin Yang, Ji Zhang, Bo Wei

Published in

Ageing research reviews. Pages 103336. Aug 24, 2026. Epub Aug 24, 2026.

Abstract

Considerable progress in oncology has substantially reduced cancer-related mortality, as reflected by the growing number of cancer survivors. In this context, the management of adverse events associated with cancer treatments has become even more important. Small-molecule VEGFR inhibitors are associated with clinically relevant cardiovascular and hepatic adverse events, including arrhythmias, heart failure, liver enzyme elevations, and hepatic failure. This review integrates the clinical profiles, organ-specific mechanisms, and shared biological pathways underlying VEGFR inhibitor-associated cardiotoxicity and hepatotoxicity. Clinical evidence primarily supports parallel cardiovascular and hepatic toxicities, whereas experimental studies identify convergent mechanisms involving endothelial injury, oxidative stress, mitochondrial dysfunction, inflammation, autophagy dysregulation, apoptosis, and metabolic disturbance. Direct evidence of cross-organ propagation was not identified in the reviewed literature, and the proposed cardio-hepatic relationship should therefore be considered a testable framework rather than an established mechanism. Particular attention is given to ageing-related susceptibility, including reduced cardiovascular and hepatic reserve, frailty, multimorbidity, and polypharmacy, which may modify treatment tolerance and monitoring needs. We also critically evaluate candidate preventive and therapeutic strategies and identify the evidence required for their clinical translation. By separating established clinical observations from mechanistic hypotheses, this review provides an evidence-graded framework for interpreting VEGFR inhibitor-associated toxicity, refining risk-adapted surveillance, directing future studies of cardio-hepatic interactions and guiding the development and validation of targeted mitigation strategies aimed at safer cancer treatment.

PMID:
42637012
Bibliographic data and abstract were imported from PubMed on 25 Aug 2026.

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