{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T17:21:32Z","timestamp":1792689692850,"version":"4.5.0"},"reference-count":171,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T00:00:00Z","timestamp":1645488000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["IG 21617"],"award-info":[{"award-number":["IG 21617"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007076","name":"Italian Association for Cancer Research","doi-asserted-by":"publisher","award":["MFAG 21956"],"award-info":[{"award-number":["MFAG 21956"]}],"id":[{"id":"10.13039\/501100007076","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>The purinergic P2X7 receptor (P2X7R) is a transmembrane protein whose expression has been related to a variety of cellular processes, while its dysregulation has been linked to inflammation and cancer. P2X7R is expressed in cancer and immune system cell surfaces. ATP plays a key role in numerous metabolic processes due to its abundance in the tumour microenvironment. P2X7R plays an important role in cancer by interacting with ATP. The unusual property of P2X7R is that stimulation with low doses of ATP causes the opening of a permeable channel for sodium, potassium, and calcium ions, whereas sustained stimulation with high doses of ATP favours the formation of a non-selective pore. The latter effect induces a change in intracellular homeostasis that leads to cell death. This evidence suggests that P2X7R has both pro- and anti-tumour proprieties. P2X7R is increasingly recognised as a regulator of inflammation. In this review, we aimed to describe the most relevant characteristics of P2X7R function, activation, and its ligands, while also summarising the role of P2X7R activation in the context of inflammation and cancer. The currently used therapeutic approaches and clinical trials of P2X7R modulators are also described.<\/jats:p>","DOI":"10.3390\/cancers14051116","type":"journal-article","created":{"date-parts":[[2022,2,22]],"date-time":"2022-02-22T22:35:09Z","timestamp":1645569309000},"page":"1116","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":93,"title":["The Role of Purinergic P2X7 Receptor in Inflammation and Cancer: Novel Molecular Insights and Clinical Applications"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5179-1525","authenticated-orcid":false,"given":"John Charles","family":"Rotondo","sequence":"first","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Centre for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Mazziotta","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Centre for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Lanzillotti","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Centre for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiara","family":"Stefani","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7951-5757","authenticated-orcid":false,"given":"Giada","family":"Badiale","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Campione","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernanda","family":"Martini","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Centre for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, 44121 Ferrara, Italy"},{"name":"Laboratory for Technologies of Advanced Therapies (LTTA), University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8269-7937","authenticated-orcid":false,"given":"Mauro","family":"Tognon","sequence":"additional","affiliation":[{"name":"Laboratories of Cell Biology and Molecular Genetics, Section of Experimental Medicine, Department of Medical Sciences, School of Medicine, University of Ferrara, 44121 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1038\/onc.2016.206","article-title":"Extracellular purines, purinergic receptors and tumor growth","volume":"36","author":"Adinolfi","year":"2017","journal-title":"Oncogene"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.imlet.2018.11.006","article-title":"Extracellular nucleotides and nucleosides as signalling molecules","volume":"205","author":"Giuliani","year":"2019","journal-title":"Immunol. 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