Kaposi's sarcoma and mTOR: a crossroad between viral infection neoangiogenesis and immunosuppression.
The incidence of Kaposi's sarcoma (KS) among the recipients of solid organ transplants is about 500 times the rate in the general population, suggesting a role for immunosuppression in the development of the disease. The drugs used for the induction and maintenance of immunosuppression and the length of treatment with these agents influence both the incidence and the type of cancer development. The clinical presentation of KS in transplant recipients is often limited to the skin. The risk of death from KS is related to the form and extent of the lesions. The main approach to managing transplant-associated KS is to reduce or even discontinue immunosuppressive therapy; this strategy carries a risk of acute rejection of the graft. KS is a multicentric tumor composed of endothelium-lined vascular spaces and spindle-shaped cells. Its pathogenesis is unclear. Recent evidence suggests that vascular endothelial growth factor (VEGF) is likely to be a growth factor for KS cells: blocking the interaction between VEGF and Flk-1/KDR can abolish VEGF-induced growth of the tumor. Recently, Sirolimus, a drug used in kidney-transplant recipients, has been suggested to reduce KS progression in transplant recipients. This unexpected effect of the drug confirms previous experimental information on KS pathogenesis and may shed light on an array of molecular mechanisms, modulated by Sirolimus, of potential clinical interest in the transplantation scenario.
Stallone
Giovanni
G
Section of Nephrology, Dialysis and Transplant, Department of Biomedical Sciences, University of Foggia, Foggia, Italy. g.stallone@ares.unifg.it
Infante
Barbara
B
Grandaliano
Giuseppe
G
Schena
Francesco Paolo
FP
Gesualdo
Loreto
L
D019288:Herpesvirus 8, Human / Q000378:metabolism*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D009389:Neovascularization, Pathologic; D016377:Organ Transplantation; D011494:Protein Kinases / Q000378:metabolism; D012514:Sarcoma, Kaposi / Q000145:classification / Q000188:drug therapy / Q000209:etiology*; D020123:Sirolimus / Q000627:therapeutic use; D012878:Skin Neoplasms / Q000145:classification / Q000188:drug therapy / Q000209:etiology*; D058570:TOR Serine-Threonine Kinases
D007166:Immunosuppressive Agents; D011494:Protein Kinases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus