Demierre Marie-France, Higgins Peter D R, Gruber Stephen B, Hawk Ernest, Lippman Scott M
Department of Dermatology, Boston University School of Medicine, 720 Harrison Avenue DOB 801A, Boston, MA 02118, USA.
Nat Rev Cancer. 2005 Dec;5(12):930-42. doi: 10.1038/nrc1751.
Randomized controlled trials for preventing cardiovascular disease indicated that statins had provocative and unexpected benefits for reducing colorectal cancer and melanoma. These findings have led to the intensive study of statins in cancer prevention, including recent, large population-based studies showing statin-associated reductions in overall, colorectal and prostate cancer. Understanding the complex cellular effects (for example, on angiogenesis and inflammation) and the underlying molecular mechanisms of statins (for example, 3-hydroxy-3-methylglutaryl coenzyme-A (HMG-CoA) reductase-dependent processes that involve geranylgeranylation of Rho proteins, and HMG-CoA-independent processes that involve lymphocyte-function-associated antigen 1) will advance the development of molecularly targeted agents for preventing cancer. This understanding might also help the development of drugs for other ageing-related diseases with interrelated molecular pathways.
预防心血管疾病的随机对照试验表明,他汀类药物在降低结直肠癌和黑色素瘤方面具有显著且意想不到的益处。这些发现促使人们对他汀类药物在癌症预防方面进行深入研究,包括近期基于大规模人群的研究显示,他汀类药物与总体癌症、结直肠癌和前列腺癌的减少有关。了解他汀类药物复杂的细胞效应(例如对血管生成和炎症的影响)及其潜在分子机制(例如涉及Rho蛋白香叶基香叶基化的3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶依赖性过程,以及涉及淋巴细胞功能相关抗原1的HMG-CoA非依赖性过程)将推动预防癌症的分子靶向药物的开发。这种认识也可能有助于开发针对其他具有相互关联分子途径的衰老相关疾病的药物。