of cancer pain and to the function of P2X7 in tumor growth and metastasis. Therapeutic implications of the administration of different P2X receptor blockers to alle- viate cancer-associated pain sensations contemporarily reducing tumor progression are also discussed. © 2014 Baishideng Publishing Group Inc. All rights reserved. Key words: Cancer; Pain; Adenosine triphosphate; P2X2; P2X3; P2X2/3; P2X4; P2X7 Core tip: Cancer pain is an increasing emergency as the number of oncological patients and survivors tends to growth. Oncological patients will greatly beneit of new therapies combining anti-tumor effects with a reduction of pain perception. This review gives an overview of latest literature on P2X receptors role in tumor progres- sion and different types of cancer pain. The potential of P2X receptors as therapeutic targets in tumor is also discussed. Franceschini A, Adinoli E. P2X receptors: New players in cancer pain. World J Biol Chem 2014; 5(4): 429-436 Available from: URL: http://www.wjgnet.com/1949-8454/full/v5/i4/429.htm DOI: http://dx.doi.org/10.4331/wjbc.v5.i4.429 INTRODUCTION Half of all oncological patients present pain symptoms [1] . This percentage arise in individuals undergoing cancer treatment getting worse, as tumor progress through its advanced stages [2-4] . Pain sensitization is also frequent in long-term cancer survivors following curative treat- ment [2,3] . Moreover, pain experience of oncological patients ranges from moderate to severe [3] . The most common pain locations in all cancer patients are back, abdomen and hips. Although there are many studies reporting an increased pain prevalence in cancer types involving head, bone, gynecological and gastrointestinal sites [2] , other meta-analysis found no signiicant relation- Alessia Franceschini, Elena Adinoli P2X receptors: New players in cancer pain MINIREVIEWS Alessia Franceschini, Elena Adinoli, Department of Morpholo- gy, Surgery and Experimental Medicine, Section of Experimental Pathology, Oncology and Biology, University of Ferrara, 44121 Ferrara, Italy Author contributions: Franceschini A and Adinoli E wrote the manuscript. Supported by Grants to Elena Adinoli from the Italian associa- tion for Cancer research (MFAG11630), and from the Region Emilia Romagna (Young researchers funds, Bando Alessandro Liberati) Correspondence to: Elena Adinoli, PhD, Assistant Profes- sor of Clinical Pathology Department of Morphology, Surgery and Experimental Medicine, Section of Experimental Pathology, Oncology and Biology, University of Ferrara, Via Borsari, 46, 44121 Ferrara, Italy. elena.adinoli@unife.it Telephone: +39-532-455445 Fax: +39-532-455351 Received: May 27, 2014 Revised: August 26, 2014 Accepted: September 16, 2014 Published online: November 26, 2014 Abstract Pain is unfortunately a quite common symptom for cancer patients. Normally pain starts as an episodic experience at early cancer phases to become chronic in later stages. In order to improve the quality of life of oncological patients, anti-cancer treatments are often accompanied by analgesic therapies. The P2X receptor are adenosine triphosphate (ATP) gated ion channels expressed by several cells including neurons, cancer and immune cells. Purinergic signaling through P2X receptors recently emerged as possible common pathway for cancer onset/growth and pain sensitivity. Indeed, tumor microenvironment is rich in extracellular ATP, which has a role in both tumor development and pain sensation. The study of the different mechanisms by which P2X receptors favor cancer progression and relative pain, represents an interesting challenge to design integrated therapeutic strategies for oncological patients. This review summarizes recent indings linking P2X receptors and ATP to cancer growth, progression and related pain. Special attention has been paid to the role of P2X2, P2X3, P2X4 and P2X7 in the genesis World J Biol Chem 2014 November 26; 5(4): 429-436 ISSN 1949-8454 (online) © 2014 Baishideng Publishing Group Inc. All rights reserved. World Journal of Biological Chemistry WJB C 429 WJBC|www.wjgnet.com November 26, 2014|Volume 5|Issue 4| Submit a Manuscript: http://www.wjgnet.com/esps/ Help Desk: http://www.wjgnet.com/esps/helpdesk.aspx DOI: 10.4331/wjbc.v5.i4.429