Zhu Shuangli, Fu Kai, Li Sijia, Yang Chuan, Pan Can, Wang Xueping, Wang Fang, Yu Xiyong, To Kenneth Kin Wah, Fu Liwu
State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Esophageal Cancer Institute, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, Guangdong, People's Republic of China.
Key Laboratory of Molecular Target & Clinical Pharmacology and the State Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & The Fifth Affiliated Hospital, Guangdong, Guangzhou Medical University, Guangzhou, 511436, China.
Exp Hematol Oncol. 2025 May 9;14(1):68. doi: 10.1186/s40164-025-00660-5.
Cancer is one of the leading causes of death worldwide. Recent advances in precision oncology have enabled many specific cancer patient populations to respond well and achieve longer survival with small-molecule kinase inhibitors, which have become a new therapeutic strategy for tumors. Since 2001, the Food and Drug Administration has approved 108 and 63 new anticancer drugs for treating solid tumors and hematological malignancies, respectively, 89 of which belong to the large group of small-molecule kinase inhibitors (SMKIs). Compared to conventional chemotherapeutic agents such as cyclophosphamide, doxorubicin, and 5-FU, SMKIs offer better efficacy with fewer toxic side effects. Nevertheless, with the development of more novel SMKIs and their wider clinical application to a larger population of cancer patients, variable degrees of cardiotoxic adverse events have emerged for some SMKIs during cancer therapy. This review comprehensively summarizes the most updated progress in the cardiotoxicity of SMKIs in cancer therapy and discusses the new findings and mechanisms, which will provide emerging strategies for the prevention of cardiotoxicity caused by small molecule targeted drugs and the design of the next generation of low cardiotoxicity targeted drugs.
癌症是全球主要死因之一。精准肿瘤学的最新进展使许多特定癌症患者群体能够通过小分子激酶抑制剂获得良好反应并实现更长生存期，小分子激酶抑制剂已成为肿瘤治疗的新策略。自2001年以来，美国食品药品监督管理局已分别批准108种和63种用于治疗实体瘤和血液系统恶性肿瘤的新型抗癌药物，其中89种属于小分子激酶抑制剂这一大类。与环磷酰胺、阿霉素和5-氟尿嘧啶等传统化疗药物相比，小分子激酶抑制剂疗效更好，毒副作用更少。然而，随着更多新型小分子激酶抑制剂的研发及其在更多癌症患者中的广泛临床应用，一些小分子激酶抑制剂在癌症治疗期间出现了不同程度的心脏毒性不良事件。本综述全面总结了小分子激酶抑制剂在癌症治疗中心脏毒性的最新进展，并讨论了新发现和机制，这将为预防小分子靶向药物引起的心脏毒性以及设计下一代低心脏毒性靶向药物提供新策略。
