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Monitoring antitumor efficacy of rapamycin in Kaposi sarcoma

Salvatore Di Paolo1, Annalisa Teutonico, Elena Ranieri

  • 1Department 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

American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation
|March 6, 2007
PubMed
Abstract

Insights

Monitoring P70 S6 kinase (P70(S6K)) activation in peripheral-blood mononuclear cells (PBMCs) can predict Kaposi sarcoma response to rapamycin. This mTOR inhibitor therapy led to skin cancer regression by reducing P70(S6K) phosphorylation.

Area of Science:

  • Oncology
  • Pharmacology
  • Immunology

Background:

  • Identifying patients who will benefit from mammalian target of rapamycin (mTOR) inhibitors like rapamycin is a clinical challenge.
  • This study investigates mTOR signaling in peripheral-blood mononuclear cells (PBMCs) of renal transplant recipients with Kaposi sarcoma.
  • The aim is to determine if PBMC signaling reflects AKT-mTOR pathway deregulation in skin cancer and predicts treatment response.

Purpose of the Study:

  • To explore mTOR signaling in PBMCs of renal transplant recipients with Kaposi sarcoma.
  • To assess if PBMC signaling correlates with AKT-mTOR pathway deregulation in skin cancer.
  • To identify patients who may benefit from rapamycin treatment and monitor their response.

Main Methods:

  • Basal and stimulated AKT and P70 S6 kinase (P70(S6K)) phosphorylation were measured in PBMCs.
  • Measurements were taken from 37 cyclosporine A-treated patients, including 10 with Kaposi sarcoma.
  • Data were collected before and 6 months after switching to rapamycin therapy.

Main Results:

  • Patients with Kaposi sarcoma exhibited elevated basal P70(S6K) activation and reduced AKT phosphorylation.
  • Rapamycin treatment significantly inhibited both AKT and P70(S6K) phosphorylation.
  • Inhibition of kinase activity paralleled the regression of Kaposi sarcoma skin lesions.

Conclusions:

  • Overactivation of basal P70(S6K) in PBMCs is associated with Kaposi sarcoma.
  • Rapamycin-induced kinase inhibition correlates with skin cancer lesion regression.
  • Monitoring P70(S6K) phosphorylation can predict and monitor rapamycin's effectiveness in renal transplant recipients with Kaposi sarcoma, aiding dose adjustment.

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