P2X7-mediated chemoprevention of epithelial cancers.
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.


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.
Case Western Reserve University, Oncology and the Comprehensive Cancer Center, Department of Reproductive Biology, Physiology and Biophysics, 11100 Euclid Avenue, Cleveland, Ohio 44106, USA. george.gorodeski@case.edu
George I
GI
Gorodeski
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D006801:Humans; D051379:Mice; D009375:Neoplasms, Glandular and Epithelial / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7; D012878:Skin Neoplasms / Q000188:drug therapy / Q000503:physiopathology / Q000517:prevention & control*; D015854:Up-Regulation / Q000187:drug effects
D000970:Antineoplastic Agents; C546468:P2RX7 protein, human; C546469:P2rx7 protein, mouse; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7