The role of mammalian target of rapamycin inhibitors in the management of post‐transplant malignancy

Abstract

Post-transplant malignancies, which occur either de novo or as cancer recurrences, are due to chronic exposure to immunosuppressive agents and are often more aggressive than those that develop in the non-transplant setting. Mammalian target of rapamycin (mTOR) inhibitors have antitumor and immunosuppressive effects. The dual effects of this class of agents may provide adequate immunosuppression to prevent organ rejection while simultaneously reducing the risk of post-transplant malignancy. mTOR inhibitors have become established approved agents for treating renal cell carcinoma and other cancers and, as reviewed herein, accumulating experience among organ transplant recipients collectively points toward a potential to prevent the development of de novo malignancies of various types in the post-transplant period. To date, most research efforts surrounding mTOR inhibitors and cancer control in the transplant population have been in the area of skin cancer prevention, but there have also been interesting observations regarding regression of post-transplant Kaposi's sarcoma and post-transplantation lymphoproliferative disorder that warrant further study.

Everolimus and Malignancy after Solid Organ Transplantation: A Clinical Update

“…Recent published reviews have assessed the evidence base relating to mTOR inhibitors overall [17, 36] but the two available agents, sirolimus and everolimus, are not necessarily interchangeable [37]. This article examines the available data and considers the role of everolimus in malignancy after organ transplantation from the clinician's perspective.…”

Donor-derived Kaposi’s sarcoma in a liver–kidney transplant recipient

“…More recently, regression of KS with less risk to the graft has been obtained by switching from calcineurin inhibitors (CNI) to sirolimus which is now considered the first‐line treatment of KS for transplant recipients . The patient with KS in this report was successfully treated by switching from tacrolimus to sirolimus which studies have shown is associated with a lower incidence of malignancy in the posttransplant period …”

Evaluation of First‐Line Sorafenib Treatment for Metastatic Renal Cell Carcinoma in Kidney Transplant Patients: A Single‐Center Experience With Four Cases

“…Osimertinib is an oral, third-generation EGFR-TKI designed to target the EGFR T790 M mutation (1)(2)(3). Osimertinib is primarily eliminated in feces (68%) and, to a lesser extent, in urine (14%) (4).…”

“…To the Editor: The risk of developing renal cancers is reportedly 3-5% among patients with end-stage renal disease pre-and post-transplantation, which is 100-fold higher than that among the general population (1). Immunosuppressive therapies, which are administered to prevent graft rejection, increase the risk of developing cancers or accelerate tumor cell growth (2). Currently, the treatment strategy for metastatic renal cell carcinoma (mRCC) consists of molecular-targeted therapy.…”