Is there a role for proliferation signal/mTOR inhibitors in the prevention and treatment of de novo malignancies after heart transplantation? Lessons learned from renal transplantation and oncology.
With the development of new immunosuppressive agents, the majority of transplant recipients are surviving for over a decade, and malignancy has become a major burden on long-term survival. Reducing the incidence of post-transplant malignancies is especially important in heart transplantation where the risk of malignancies is higher than in other organ transplants. Everolimus and sirolimus, the proliferation signal inhibitors (PSIs) or mammalian target-of-rapamycin (mTOR) inhibitors, now provide new strategies for immunosuppression because of their proven efficacy that translates to a reduction in doses of calcineurin inhibitors needed to prevent acute rejection. In addition, the anti-proliferative effects of this class of drugs raise the possibility that they may be effective for reducing the risk of malignancies after solid-organ transplantation. Despite the paucity of direct clinical evidence for this effect in heart transplant patients, observations from renal transplant recipients suggest that the anti-proliferative actions of PSIs/mTOR inhibitors may also protect against malignancies in heart transplant recipients. This potential for an anti-cancer effect is further supported by the emerging data on the use of PSIs/mTOR inhibitors in non-transplant oncology patients. Reviewed in this article are the incidence rates of malignancies after solid-organ transplantation, and the evidence for anti-cancer effects of PSIs/mTOR inhibitors in renal transplant recipients and in non-transplant patients. Also discussed are the implications of these observational data for future studies on the reduction of malignancies after heart transplantation.
Valantine
Hannah
H
Falk Cardiovascular Research Center, Stanford University Medical School, Stanford, California 94305, USA. hvalantine@stanford.edu
D001379:Azathioprine / Q000009:adverse effects; D016572:Cyclosporine / Q000009:adverse effects; D004791:Enzyme Inhibitors / Q000009:adverse effects*; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects*; D016030:Kidney Transplantation / Q000009:adverse effects*; D009369:Neoplasms / Q000453:epidemiology* / Q000517:prevention & control*; D011183:Postoperative Complications / Q000453:epidemiology; D011494:Protein Kinases / Q000378:metabolism*; D012306:Risk; D012307:Risk Factors; D058570:TOR Serine-Threonine Kinases; D016559:Tacrolimus / Q000009:adverse effects
D004791:Enzyme Inhibitors; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D001379:Azathioprine; D016559:Tacrolimus