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Updated: Aug 6, 2026
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A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Kinase Inhibitor Cardiotoxicity Database (KICDB): a causality-oriented multi-omics database for kinase
Jiamin Wei1, Yin Liu2, Miaoqing Wu3
1Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
British Journal of Pharmacology
|July 17, 2026
Summary
Kinase inhibitors (KIs) used in cancer therapy can cause heart damage. Our new database, KICDB, integrates transcriptomic data and causal inference to uncover mechanisms of KI-induced cardiotoxicity and identify potential protective factors.
Area of Science:
- Cardiovascular research
- Pharmacogenomics
- Cancer therapy
Background:
- Kinase inhibitors (KIs) are crucial for targeted cancer therapy.
- KI-induced cardiotoxicity presents a significant clinical challenge, limiting treatment efficacy.
- A systematic approach is needed to understand the causal mechanisms of KI cardiotoxicity.
Purpose of the Study:
- To develop a comprehensive resource for exploring the molecular determinants of kinase inhibitor-induced cardiotoxicity.
- To integrate large-scale transcriptomic data with causal inference methods.
- To identify shared mechanisms and genetic factors contributing to KI cardiotoxicity.
Main Methods:
- Development of the Kinase Inhibitor Cardiotoxicity Database (KICDB).
- Large-scale transcriptomic meta-analysis of 5291 samples.
- Causal inference, including Mendelian randomization (MR) analysis.
Main Results:
- A shared mechanism of KI cardiotoxicity involves disruption of cellular mitosis, including chromosome segregation and nuclear division.
- Mendelian randomization identified 26 causal associations linking specific kinase targets (e.g., RNF13, TIE1) to cardiovascular disease risk.
- TYRO3 and JAK2 were identified as potentially cardioprotective kinase targets.
Conclusions:
- KICDB offers a mechanistic framework connecting transcriptomic changes to genetically validated causal factors in KI cardiotoxicity.
- This resource facilitates biomarker discovery and mechanistic exploration for developing cardioprotective strategies.
- KICDB aids in designing safer kinase inhibitors and personalized cancer treatments.
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