Immunosuppression and tumor development in organ transplant recipients: the emerging dualistic role of rapamycin.
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.
Gaumann
Andreas
A
Institute of Pathology, University Regensburg, Regensburg, Germany.
Schlitt
Hans J
HJ
Geissler
Edward K
EK
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D006801:Humans; D007165:Immunosuppression Therapy / Q000379:methods*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009369:Neoplasms / Q000453:epidemiology* / Q000517:prevention & control; D011183:Postoperative Complications / Q000517:prevention & control; D011494:Protein Kinases / Q000187:drug effects / Q000378:metabolism; D020123:Sirolimus / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases; D014181:Transplantation Immunology
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus