Dang Yexing, Zhang Yu, Wang Zhihao
Department of Geriatrics, Jilin Geriatrics Clinical Research Center, The First Hospital of Jilin University, Changchun, China.
Front Pharmacol. 2025 May 14;16:1578345. doi: 10.3389/fphar.2025.1578345. eCollection 2025.
Statins, widely recognized as a cornerstone in the prevention of cardiovascular diseases, have garnered increasing attention in oncology due to their pleiotropic effects, particularly their potential roles in regulating breast and colorectal cancer. Emerging evidence suggests that statins may exert anticancer effects through multiple mechanisms, including the mitochondrial apoptosis pathway, the LKB1-AMPK-p38MAPK-p53-survivin signaling cascade, inhibition of the mevalonate pathway, modulation of the EGFR/RhoA and IGF-1 signaling pathways, and regulation of the BMP/SMAD4 signaling pathway. However, significant heterogeneity exists in the reported anticancer effects of statins, likely due to variations in statin type (lipophilic vs hydrophilic), dosage, treatment duration, and population-specific characteristics. These factors contribute to inconsistencies in study outcomes. Additionally, while combination therapies incorporating statins with chemotherapy and immunotherapy have demonstrated synergistic effects in certain studies, their clinical utility remains to be fully established. Nevertheless, current evidence suggests that statins may have a potential role in reducing breast and colorectal cancer-related mortality. Future research should prioritize elucidating their precise molecular mechanisms, defining dose-response relationships, developing personalized treatment strategies within the framework of precision medicine, and validating their efficacy through large-scale, long-term prospective studies. These efforts will provide a more robust scientific foundation for the clinical application of statins in oncology. This review systematically explores the role of statins in breast and colorectal cancer regulation, covering clinical evidence, underlying biological mechanisms, pharmacological distinctions, synergistic therapeutic potential, and translational medicine prospects.
他汀类药物被广泛认为是预防心血管疾病的基石，由于其多效性作用，尤其是在调节乳腺癌和结直肠癌方面的潜在作用，在肿瘤学领域受到了越来越多的关注。新出现的证据表明，他汀类药物可能通过多种机制发挥抗癌作用，包括线粒体凋亡途径、LKB1-AMPK-p38MAPK-p53-生存素信号级联、甲羟戊酸途径的抑制、EGFR/RhoA和IGF-1信号通路的调节以及BMP/SMAD4信号通路的调节。然而，他汀类药物报道的抗癌效果存在显著异质性，这可能是由于他汀类药物类型（亲脂性与亲水性）、剂量、治疗持续时间和人群特异性特征的差异所致。这些因素导致研究结果不一致。此外，虽然在某些研究中，将他汀类药物与化疗和免疫疗法联合使用已显示出协同作用，但其临床实用性仍有待充分确立。尽管如此，目前的证据表明，他汀类药物可能在降低乳腺癌和结直肠癌相关死亡率方面具有潜在作用。未来的研究应优先阐明其精确的分子机制，确定剂量反应关系，在精准医学框架内制定个性化治疗策略，并通过大规模、长期前瞻性研究验证其疗效。这些努力将为他汀类药物在肿瘤学中的临床应用提供更坚实的科学基础。本综述系统地探讨了他汀类药物在乳腺癌和结直肠癌调节中的作用，涵盖临床证据、潜在生物学机制、药理学差异、协同治疗潜力和转化医学前景。
