{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T06:29:04Z","timestamp":1778135344633,"version":"3.51.4"},"reference-count":68,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T00:00:00Z","timestamp":1663200000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005727","name":"Universidade de Coimbra","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005727","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Chem."],"abstract":"<jats:p>Ubiquitin-specific protease 7 (USP7) is a member of one of the most largely studied families of deubiquitylating enzymes. It plays a key role modulating the levels of multiple proteins, including tumor suppressors, transcription factors, epigenetic modulators, DNA repair proteins, and regulators of the immune response. The abnormal expression of USP7 is found in various malignant tumors and a high expression signature generally indicates poor tumor prognosis. This suggests USP7 as a promising prognostic and druggable target for cancer therapy. Nonetheless, no approved drugs targeting USP7 have already entered clinical trials. Therefore, the development of potent and selective USP7 inhibitors still requires intensive research and development efforts before the pre-clinical benefits translate into the clinic. This mini review systematically summarizes the role of USP7 as a drug target for cancer therapeutics, as well as the scaffolds, activities, and binding modes of some of the most representative small molecule USP7 inhibitors reported in the scientific literature. To wind up, development challenges and potential combination therapies using USP7 inhibitors for less tractable tumors are also disclosed.<\/jats:p>","DOI":"10.3389\/fchem.2022.1005727","type":"journal-article","created":{"date-parts":[[2022,9,15]],"date-time":"2022-09-15T08:20:39Z","timestamp":1663230039000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Highlights in USP7 inhibitors for cancer treatment"],"prefix":"10.3389","volume":"10","author":[{"given":"Rita I.","family":"Oliveira","sequence":"first","affiliation":[]},{"given":"Romina A.","family":"Guedes","sequence":"additional","affiliation":[]},{"given":"Jorge A. 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