Immunosuppression and tumor development in organ transplant recipients: the emerging dualistic role of rapamycin

被引:39
作者
Gaumann, Andreas [2 ]
Schlitt, Hans J. [1 ]
Geissler, Edward K. [1 ]
机构
[1] Univ Regensburg, Dept Surg, D-93053 Regensburg, Germany
[2] Univ Regensburg, Inst Pathol, D-93053 Regensburg, Germany
关键词
cancer; mammalian target of rapamycin; rapamycin; transplantation;
D O I
10.1111/j.1432-2277.2007.00610.x
中图分类号
R61 [外科手术学];
学科分类号
摘要
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.
引用
收藏
页码:207 / 217
页数:11
相关论文
共 86 条
[1]   Percutaneous coronary revascularization using a trilayer metal phosphorylcholine-coated zotarolimus-eluting stent [J].
Abizaid, Alexandre ;
Lansky, Alexandra J. ;
Fitzgerald, Peter J. ;
Tanajura, Luis Fernando ;
Feres, Fausto ;
Staico, Rodolfo ;
Mattos, Luiz ;
Abizaid, Andrea ;
Chaves, Aurea ;
Centemero, Marinella ;
Sousa, Amanda G. M. R. ;
Sousa, J. Eduardo ;
Zaugg, Margo J. ;
Schwartz, Lewis B. .
AMERICAN JOURNAL OF CARDIOLOGY, 2007, 99 (10) :1403-1408
[2]   Randomized phase II study of multiple dose levels of CCI-779, a novel mammalian target of rapamycin kinase inhibitor, in patients with advanced refractory renal cell carcinoma [J].
Atkins, MB ;
Hidalgo, M ;
Stadler, WM ;
Logan, TF ;
Dutcher, JP ;
Hudes, GR ;
Park, Y ;
Lion, SH ;
Marshall, B ;
Boni, JP ;
Dukart, G ;
Sherman, ML .
JOURNAL OF CLINICAL ONCOLOGY, 2004, 22 (05) :909-918
[3]   The hypoxic microenvironment of the skin contributes to Akt-mediated melanocyte transformation [J].
Bedogni, B ;
Welford, SM ;
Cassarino, DS ;
Nickoloff, BJ ;
Giaccia, AJ ;
Powell, MB .
CANCER CELL, 2005, 8 (06) :443-454
[4]   PML inhibits HIF-1α translation and neoangiogenesis through repression of mTOR [J].
Bernardi, Rosa ;
Guernah, Ilhem ;
Jin, David ;
Grisendi, Silvia ;
Alimonti, Andrea ;
Teruya-Feldstein, Julie ;
Cordon-Cardo, Carlos ;
Simon, M. Celeste ;
Rafii, Shahin ;
Pandolfi, Pier Paolo .
NATURE, 2006, 442 (7104) :779-785
[5]   The mTOR inhibitor RAD001 sensitizes tumor cells to DNA-damaged induced apoptosis through inhibition of p21 translation [J].
Beuvink, I ;
Boulay, A ;
Fumagalli, S ;
Zilbermann, F ;
Ruetz, S ;
O'Reilly, T ;
Natt, F ;
Hall, J ;
Lane, HA ;
Thomas, G .
CELL, 2005, 120 (06) :747-759
[6]   Dysregulation of HIF and VEGF is a unifying feature of the familial hamartoma syndromes [J].
Brugarolas, J ;
Kaelin, WG .
CANCER CELL, 2004, 6 (01) :7-10
[7]   TSC2 regulates VEGF through mTOR-dependent and -independent pathways [J].
Brugarolas, JB ;
Vazquez, F ;
Reddy, A ;
Sellers, WR ;
Kaelin, WG .
CANCER CELL, 2003, 4 (02) :147-158
[8]  
CALNE RY, 1989, LANCET, V2, P227
[9]   Conversion to sirolimus: A successful treatment for posttransplantation Kaposi's sarcoma [J].
Campistol, JM ;
Gutierrez-Dalmau, A ;
Torregrosa, JV .
TRANSPLANTATION, 2004, 77 (05) :760-762
[10]   Phase II study of temsirolimus (CCI-779), a novel inhibitor of mTOR, in heavily pretreated patients with locally advanced or metastatic breast cancer [J].
Chan, S ;
Scheulen, ME ;
Johnston, S ;
Mross, K ;
Cardoso, F ;
Dittrich, C ;
Eiermann, W ;
Hess, D ;
Morant, R ;
Semiglazov, V ;
Borner, M ;
Salzberg, M ;
Ostapenko, V ;
Illiger, HJ ;
Behringer, D ;
Bardy-Bouxin, N ;
Boni, J ;
Kong, S ;
Cincotta, M ;
Moore, L .
JOURNAL OF CLINICAL ONCOLOGY, 2005, 23 (23) :5314-5322