Department of Chemistry, Materials and Chemical Engineering "Giulio Natta", Politecnico di Milano, Milan, Italy.
Department of Electronics, Information and Bioengineering, Politecnico di Milano, Milan, Italy.
Sci Rep. 2024 Aug 31;14(1):20298. doi: 10.1038/s41598-024-71240-6.
Statins, widely used cardiovascular drugs that lower cholesterol by inhibiting HMG-CoA reductase, have been increasingly recognized for their potential anticancer properties. This study elucidates the underlying mechanism, revealing that statins exploit Synthetic Lethality, a principle where the co-occurrence of two non-lethal events leads to cell death. Our computational analysis of approximately 37,000 SL pairs identified statins as potential drugs targeting genes involved in SL pairs with metastatic genes. In vitro validation on various cancer cell lines confirmed the anticancer efficacy of statins. This data-driven drug repurposing strategy provides a molecular basis for the anticancer effects of statins, offering translational opportunities in oncology.
他汀类药物是一种广泛应用于心血管疾病的药物，通过抑制 HMG-CoA 还原酶降低胆固醇水平，其抗癌特性也逐渐得到了认可。本研究阐明了其潜在的作用机制，表明他汀类药物利用了合成致死性（Synthetic Lethality），即两种非致死性事件同时发生导致细胞死亡的原理。我们对大约 37000 对 SL 对的计算分析表明，他汀类药物可能是针对具有转移基因的 SL 对中涉及的基因的潜在药物。在各种癌细胞系中的体外验证证实了他汀类药物的抗癌功效。这种基于数据的药物再利用策略为他汀类药物的抗癌作用提供了分子基础，为肿瘤学领域提供了转化机会。
