Immunosuppressants and skin cancer in transplant patients: focus on rapamycin.
BACKGROUND
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.


OBJECTIVE
This article will discuss the role of the main immunosuppressants in the pathogenesis of skin cancers.


METHODS
This work consists of a review of the most significant publications.


RESULTS
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.


CONCLUSIONS
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.
Euvrard
Sylvie
S
Department of Dermatology, Edouard Herriott Hospital, Lyon, France. sylvie.euvrard@numericable.fr
Ulrich
Claas
C
Lefrancois
Nicole
N
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D051379:Mice; D009389:Neovascularization, Pathologic / Q000517:prevention & control; D016377:Organ Transplantation / Q000009:adverse effects; D020123:Sirolimus / Q000008:administration & dosage*; D012878:Skin Neoplasms / Q000209:etiology / Q000517:prevention & control*
D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D020123:Sirolimus