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A large body of evidence demonstrates the dependency of several tumors such as breast, prostate, ovary, thyroid, glioblastoma and LUAD, on the activity of COPZ1, a component of the heptameric COPI complex. Thus, COPZ1 is emerging as a potential novel therapeutic target for tumors of different origin. In different tumor models COPZ1 inhibition was found implicated in abortive autophagy, ER stress and activation of ferroptosis. In this review we summarize the different studies characterizing COPZ1 as a NOA gene in different tumor types, and discuss potential issues related to its targeting.<\/jats:p>","DOI":"10.3389\/fphar.2025.1636326","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T05:36:45Z","timestamp":1757050605000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["COPZ1: an example of non-oncogene addiction in human tumors"],"prefix":"10.3389","volume":"16","author":[{"given":"Tiziana","family":"Di Marco","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Debora","family":"Vergaro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela","family":"Greco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"34629","DOI":"10.18632\/oncotarget.5282","article-title":"Identification of thyroid tumor cell vulnerabilities through a siRNA-based functional screening","volume":"6","author":"Anania","year":"2015","journal-title":"Oncotarget"},{"key":"B2","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/j.canlet.2017.09.024","article-title":"Targeting COPZ1 non-oncogene addiction counteracts the viability of thyroid tumor cells","volume":"410","author":"Anania","year":"2017","journal-title":"Cancer Lett."},{"key":"B3","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1186\/s12967-021-03218-1","article-title":"Identification of COPA as a potential prognostic biomarker and pharmacological intervention target of cervical cancer by quantitative proteomics and experimental verification","volume":"20","author":"Bao","year":"2022","journal-title":"J. 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