Authors
Jiamin Wei, Yin Liu, Miaoqing Wu, Guoyuan Li, Xinyao Zheng, Huafeng Fu, Jian Zhang, Jijin Lin
Published in
British journal of pharmacology. Jul 17, 2026. Epub Jul 17, 2026.
Abstract
Kinase inhibitors (KIs) are essential in targeted cancer therapy but frequently cause cardiotoxicity, limiting their clinical utility. A systematic resource to explore the underlying causal mechanisms is urgently needed.
We developed the Kinase Inhibitor Cardiotoxicity Database (KICDB ), an interactive web platform integrating large-scale transcriptomic meta-analysis with causal inference to identify molecular determinants of KI-induced cardiotoxicity.
Meta-analysis of 5291 samples revealed a convergent disruption of the cellular mitotic machinery, specifically chromosome segregation and nuclear division, as a shared mechanism of toxicity across multiple KI classes. Furthermore, Mendelian randomization (MR) analysis identified 26 robust causal associations, linking specific kinase targets (e.g. RING finger protein 13 [RNF13] and tyrosine kinase with immunoglobulin like and EGF like domains 1 [TIE1]) to increased risks of cardiomyopathy and myocardial infarction, while identifying TYRO3 protein tyrosine kinase [Tyro3] and Janus kinase 2 (JAK2) as potential cardioprotective factors.
KICDB provides a mechanistic framework linking transcriptomic perturbations with genetically validated causal drivers. By linking transcriptomic perturbations with causal validation, it serves as a resource to advance biomarker discovery, mechanistic exploration and the design of cardioprotective strategies.
PMID:
42464730
Bibliographic data and abstract were imported from PubMed on 17 Jul 2026.
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