{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:10:44Z","timestamp":1790777444134,"version":"4.1.0"},"reference-count":51,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,12,22]],"date-time":"2025-12-22T00:00:00Z","timestamp":1766361600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health to cover publication costs"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Murine Double Minute 2 (MDM2) gene encodes an E3 ubiquitin ligase that negatively regulates the tumor suppressor p53, maintaining low p53 levels through ubiquitination and proteasomal degradation. MDM2 overexpression in various malignancies leads to reduced p53 activity, contributing to tumor initiation and resistance to therapies. As such, MDM2 is a promising target for drug development. Innovative small-molecule inhibitors are being designed to disrupt the MDM2-p53 interaction, thereby restoring p53\u2019s tumor-suppressive functions. This review focuses on clinical trials evaluating MDM2 inhibition for cancer therapy. MDM2 exerts its oncogenic effects primarily through its interaction with p53 but also has p53-independent functions involved in cell cycle progression and DNA repair. Elevated MDM2 expression is associated with poor prognosis across various cancers, including dedifferentiated liposarcoma, breast cancer, and glioblastoma. Targeting MDM2 with inhibitors has shown promising potential in clinical development, aiming to reactivate p53\u2019s functions in tumors with wild-type TP53, improving therapeutic outcomes in cancer treatment.<\/jats:p>","DOI":"10.3390\/ijms27010099","type":"journal-article","created":{"date-parts":[[2025,12,26]],"date-time":"2025-12-26T03:06:02Z","timestamp":1766718362000},"page":"99","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["MDM2 in Tumor Biology and Cancer Therapy: A Review of Current Clinical Trials"],"prefix":"10.3390","volume":"27","author":[{"given":"Francesco","family":"Russano","sequence":"first","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3944-0313","authenticated-orcid":false,"given":"Mattia","family":"Sturlese","sequence":"additional","affiliation":[{"name":"Molecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1564-2594","authenticated-orcid":false,"given":"Luigi","family":"Dall\u2019Olmo","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9594-5178","authenticated-orcid":false,"given":"Francesco","family":"Callegarin","sequence":"additional","affiliation":[{"name":"Clinical Research Unit, Veneto Institute of Oncology IOV-IRCCS, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9709-977X","authenticated-orcid":false,"given":"Davide","family":"Brugnolo","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2862-8014","authenticated-orcid":false,"given":"Paolo","family":"Del Fiore","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vittoria","family":"Patti","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianna","family":"Purpura","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7514-3802","authenticated-orcid":false,"given":"Stefano","family":"Moro","sequence":"additional","affiliation":[{"name":"Molecular Modeling Section, Department of Pharmaceutical and Pharmacological Sciences, University of Padua, 35131 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Rastrelli","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9433-8445","authenticated-orcid":false,"given":"Simone","family":"Mocellin","sequence":"additional","affiliation":[{"name":"Soft-Tissue, Peritoneum and Melanoma Surgical Oncology Unit, Veneto Institute of Oncology (IOV), 35128 Padua, Italy"},{"name":"Department of Surgery, Oncology and Gastroenterology (DISCOG), University of Padua, 35128 Padua, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nrc3430","article-title":"MDM2, MDMX and p53 in oncogenesis and cancer therapy","volume":"13","author":"Wade","year":"2013","journal-title":"Nat. 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