Gaumann Andreas, Schlitt Hans J, Geissler Edward K
Institute of Pathology, University Regensburg, Regensburg, Germany.
Transpl Int. 2008 Mar;21(3):207-17. doi: 10.1111/j.1432-2277.2007.00610.x. Epub 2007 Dec 5.
Cancer morbidity and mortality are increasingly apparent risks in transplant recipients, thus reducing life quality and overall survival. These risks have largely been attributed to long-term immunosuppressive drug therapy, which remains necessary to prevent organ allograft rejection. Interestingly, however, recent studies challenge the premise that all immunosuppressive drugs necessarily promote cancer. A particular class of immunosuppressants, referred to as mammalian target of rapamycin (mTOR) inhibitors, has been shown to have potent anti-cancer effects that are presently being tested in clinical studies. The focus of this review is to present current evidence that allows us to understand better the dual immunosuppressive and anti-cancer functions of this class of drugs used to prevent allograft rejection. We will concentrate on the different functions of mTOR that allow it to simultaneously control the immune system and tumor development. We will also discuss results from current clinical studies that either support or refute this potential dualistic role.
癌症发病率和死亡率在移植受者中日益成为明显的风险,从而降低了生活质量和总体生存率。这些风险在很大程度上归因于长期免疫抑制药物治疗,而这种治疗对于预防器官移植排斥反应仍然是必要的。然而,有趣的是,最近的研究对所有免疫抑制药物必然会促进癌症这一前提提出了质疑。一类特定的免疫抑制剂,称为雷帕霉素靶蛋白(mTOR)抑制剂,已被证明具有强大的抗癌作用,目前正在临床研究中进行测试。本综述的重点是展示当前的证据,使我们能够更好地理解这类用于预防移植排斥反应的药物的双重免疫抑制和抗癌功能。我们将专注于mTOR的不同功能,这些功能使其能够同时控制免疫系统和肿瘤发展。我们还将讨论当前临床研究中支持或反驳这种潜在双重作用的结果。