Immunosuppressants and Skin Cancer in Transplant Patients: Focus on Rapamycin

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Abstract
The responsibility of immunosuppressants for the increased risk of skin cancers in organ transplant recipients is widely recognized. Discerning the role of each drug is complicated owing to the fact that most patients generally have combinations of several medications. This article will discuss the role of the main immunosuppressants in the pathogenesis of skin cancers. This work consists of a review of the most significant publications. Experimental and clinical studies suggest that corticosteroids, azathioprine, cyclosporine (CsA), and tacrolimus increase the incidence of skin cancer. Each drug may act through two different mechanisms including the impairment of the systemic immunosurveillance and a direct oncogenic effect. CsA was shown to be oncogenic independently of its immunosuppressive effect. By contrast, several works on mice have found that rapamycin inhibits tumor growth while being immunosuppressive. Furthermore, rapamycin was shown to inhibit several UV-induced mechanisms involved in skin carcinogenesis. Preliminary clinical studies have reported a lower incidence of skin malignancy in patients treated with rapamycin compared to CsA from the time of transplantation. New immunosuppressive strategies for transplant patients with skin cancer are not only based on minimizing immunosuppression. Data suggest that rapamycin could have a protective effect against skin cancer. Further studies are required to assess accurately the efficacy and tolerance of rapamycin in these patients.