Use of proliferation signal inhibitors in the management of post-transplant malignancies--clinical guidance.
Increasing success in renal transplantation and longer patient survival has meant that post-transplant malignancies are having an increasing impact on long-term graft and patient survival. Choice of the immunosuppressive agents provides one of the controllable risk factors for the development of malignancies in this population. Calcineurin inhibitors (CNIs) are associated with an increased incidence of cancers, whereas the proliferation signal inhibitors (PSIs), everolimus and sirolimus have demonstrated anti-oncogenic effects in pre-clinical models and are currently being investigated as anti-cancer agents in clinical trials. There is increasing evidence demonstrating a lower incidence of post-transplant malignancies in renal transplant recipients receiving PSI-based immunosuppression compared with those receiving CNIs. Conversion from CNIs to PSIs has been shown to lead to the regression of Kaposi's sarcoma in renal transplant recipients and is now part of accepted standard care for this tumour in this setting. The anti-cancer properties of PSI-based regimens have the potential to combine the dual benefits of immunosuppression without the use of CNIs and the direct anti-oncogenic effects through their inhibition of the mammalian target of rapamycin (mTOR) signalling pathway. In the absence of formal clinical trial evidence on the best way to use PSIs in this setting, a workshop was held to provide practical guidance on immunosuppressive strategies in the context of malignancy, given the current state of knowledge.
Campistol
Josep M
JM
Servei de Nefrologia I Transplantament Renal, Renal Transplant Unit, Hospital Clinic, Universitat de Barcelona, 170, Villarroel, Spain.
Albanell
Joan
J
Arns
Wolfgang
W
Boletis
Ioannis
I
Dantal
Jacques
J
de Fijter
J W
JW
Mortensen
Svend Aage
SA
Neumayer
Hans-Hellmut
HH
Øyen
Ole
O
Pascual
Julio
J
Pohanka
Erich
E
Schena
F Paolo
FP
Serón
Daniel
D
Sparacino
Vito
V
Chapman
Jeremy R
JR
D065095:Calcineurin Inhibitors; D000068338:Everolimus; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D016030:Kidney Transplantation / Q000009:adverse effects*; D009369:Neoplasms / Q000188:drug therapy* / Q000209:etiology; D011494:Protein Kinases / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*; D020123:Sirolimus / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D058570:TOR Serine-Threonine Kinases
D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D000068338:Everolimus; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus