Skin Cancer Research Today is a free monthly online journal that collates and summarizes the latest research about Skin Cancer, including details on identification, causes, prevention, treatment.

Monitoring antitumor efficacy of rapamycin in Kaposi sarcoma.

Di Paolo S, Teutonico A, Ranieri E, Gesualdo L, Schena PF

Department of Emergency and Organ Transplants, Division of Nephrology, Dialysis and Transplantation, University of Bari, Policlinico-Piazza Giulio Cesare, 11-70124 Bari, Italy. s.dipaolo@nephro.uniba.it

BACKGROUND: The clinical challenge for the application of rapamycin and its derivatives as anticancer drugs is the ability to prospectively identify which tumors will be sensitive to mammalian target of rapamycin (mTOR) inhibition. The present study is designed to explore mTOR signaling in peripheral-blood mononuclear cells (PBMCs) from renal transplant recipients with Kaposi sarcoma and ascertain whether it would reflect deregulation of the AKT-mTOR pathway in skin cancer tissue and might help identify which patients would benefit from rapamycin treatment, as well as to monitor their clinical response. METHODS: We measured basal and in vivo stimulated AKT and P70 S6 kinase (P70(S6K)) phosphorylation in PBMCs from 37 cyclosporine A-treated patients, 10 of whom had Kaposi sarcoma, before and 6 months after conversion to rapamycin therapy. RESULTS: Patients with Kaposi sarcoma showed markedly increased basal P70(S6K) activation and depressed phosphorylation of AKT. Long-term treatment with rapamycin was associated with marked inhibition of basal and stimulated phosphorylation of both AKT and P70(S6K), in parallel with regression of the dermal neoplasm. CONCLUSION: Overactivation of basal P70(S6K) in PBMCs from renal transplant recipients appears to be associated with the presence of Kaposi sarcoma dermal lesions; conversely, kinase inhibition is linked to regression of skin cancer lesions. Thus, monitoring P70(S6K) phosphorylation can help predict and monitor the biological effectiveness of rapamycin in renal transplant recipients with Kaposi sarcoma and possibly adjust the biologically active doses of the mTOR inhibitor.

Published 5 March 2007 in Am J Kidney Dis, 49(3): 462-70.
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