P2X7-mediated chemoprevention of epithelial cancers

Abstract

Background: Anti-apoptotic mechanisms contribute to the development of cancer. The purinergic ligand-gated ion channel receptor P2X(7) system is an important pro-apoptosis modulator in epithelial cells, and augmentation of P2X(7)-mediated apoptosis has been proposed as a novel pharmacological modality for chemoprevention and treatment of epithelial cancers.

Objective: This review focuses on the progress towards clinical application of therapies that directly modulate P2X(7)-mediated apoptosis. This paper reviews and discusses P2X(7)-mediated apoptosis in the context of prevention and growth-control of epithelial cancer cells, and summarizes recent data in the mouse skin model in vivo.

Methods: Data for this review were identified from the PubMed and MEDLINE databases.

Summary/conclusions: The growing understanding of mechanisms of P2X(7)-mediated apoptosis has generated a novel strategy for targeting directly and specifically skin neoplasia. The data link directly, for the first time, upregulation of apoptosis with cancer chemoprevention. Striking antitumor efficacy has been achieved in the rodent cancer model, and it is likely that the recently gained wealth of knowledge about the mechanisms of P2X(7)-control of apoptosis will eventually be translated into new clinical therapies for epithelial cancers.