The role of mTOR inhibitors in the management of posttransplant malignancy.
Organ transplant recipients given mammalian target of rapamycin inhibitor (mTORi) have reduced incidence of de novo posttransplant malignancies (dNPTMs). Posttransplant Kaposi's sarcoma and nonmelanotic skin malignancies (NMSC) frequently undergo remission/regression after conversion to mTORi immunosuppression (IS), especially early, small, and low-grade lesions, whereas larger, aggressive, and metastatic skin tumors are less likely to respond. mTORi-based IS is effective and well tolerated in orthotopic liver transplant patients with hepatocellular carcinoma (HCC) achieving excellent survival and disease-free intervals, particularly with extended criteria tumors, although the evidence that mTORi prevents HCC recurrence after orthotopic liver transplantation is only suggestive. Regression of metastatic HCC and other tumors and various forms of posttransplant lymphoproliferative disease have occurred after mTOR conversion. Documentation of regression/remission of other solid-organ dNPTM (colon, stomach, breast, etc.) after mTORi conversion is essentially absent with only anecdotal reports lacking follow-up data. Unfortunately, there is not a single reported prospective clinical trial powered for looking at the effect of mTORi IS in transplant recipients. Nevertheless, reduced incidence of all of dNPTMs and remission/regression of the commonest posttransplant tumors with mTOR therapy are strong reasons to expand the use of mTORi.
Monaco
Anthony P
AP
The Transplant Center, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. amonaco@bidmc.harvard.edu
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D065095:Calcineurin Inhibitors; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy / Q000209:etiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008113:Liver Neoplasms / Q000188:drug therapy / Q000209:etiology; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000209:etiology; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology; D047428:Protein Kinase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D011494:Protein Kinases / Q000378:metabolism*; D012514:Sarcoma, Kaposi / Q000188:drug therapy / Q000209:etiology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000209:etiology; D058570:TOR Serine-Threonine Kinases; D014180:Transplantation / Q000009:adverse effects*
D000970:Antineoplastic Agents; D065095:Calcineurin Inhibitors; D007166:Immunosuppressive Agents; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases