Stallone G et al. (2005) Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 352: 1317–1323

Immunosuppression is thought to be important in the natural history of Kaposi's sarcoma, and the disease is 500 times more prevalent in patients who have received a solid-organ transplant than in the general population. In such patients, the skin lesions associated with Kaposi's sarcoma can be controlled by reducing immunosuppressive therapy, but this increases the risk of graft rejection.

The immunosuppressive drug sirolimus (rapamycin) is reported to inhibit tumorigenesis by suppressing VEGF expression and disrupting the Akt–p70S6 signaling pathway; therefore, this compound has therapeutic potential for immunosuppression-related malignancies. Stallone and co-workers have recently investigated the antineoplastic properties of sirolimus in kidney-transplant recipients with Kaposi's sarcoma.

Between October 2001 and March 2004, 15 kidney-graft recipients (mean age 48.7 years) on identical immunosuppressive drug regimens were enrolled in the study. All patients were HIV negative. Immunosuppressive therapy was changed from cyclosporine, mycophenolate mofetil and prednisone to sirolimus and prednisone when Kaposi's sarcoma was diagnosed. Biopsies of lesions and normal skin were taken at diagnosis and analyzed for VEGF, Flk-1/KDR protein, phosphorylated Akt and p70S6 kinase, which were all found to be present in significantly higher levels in Kaposi's sarcoma cells than in normal skin cells. After 3 months of sirolimus therapy, cutaneous lesions were undetectable in all patients. Biopsies taken from the site of the original lesion, 6 months after sirolimus therapy was initiated, confirmed that all patients had attained clinical remission of Kaposi's sarcoma with no incidents of graft rejection. The authors conclude that sirolimus is effective in treating Kaposi's sarcoma in kidney-transplant patients, while maintaining an immunosuppressive effect.