{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,25]],"date-time":"2025-11-25T05:58:53Z","timestamp":1764050333223,"version":"3.45.0"},"reference-count":131,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2025,11,23]],"date-time":"2025-11-23T00:00:00Z","timestamp":1763856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005010","name":"Italian Association for Cancer Research","doi-asserted-by":"crossref","award":["#30710"],"award-info":[{"award-number":["#30710"]}],"id":[{"id":"10.13039\/501100005010","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In the context of precision oncology, understanding the molecular drivers of colorectal cancer (CRC) is critical for improving prognosis and guiding targeted therapy. FBXW7 is a tumor suppressor that plays a pivotal role in CRC by regulating the degradation of key oncogenic proteins, influencing tumor initiation, growth, therapeutic response, and metastatic behavior. Mutations in FBXW7 occur in 6\u201310% of CRC. Despite its biological relevance, the prognostic and predictive role of FBXW7 in CRC remains unclear, with inconsistent findings across studies. This systematic review collects and analyzes current evidence on FBXW7 mutations and expression in CRC, emphasizing its potential role in risk stratification, therapeutic response, and personalized treatment approaches. A total of 113 records were selected on PubMed, SCOPUS, Web of Science and Cochrane Central Register of Controlled Trials from 2015 and January 2025, of which 48 examined the preclinical landscape of FBXW7 in CRC and 65 focused on its clinical role. FBXW7 mutations are associated with different clinicopathological patterns, including early-onset disease, microsatellite instability, and co-occurring driver alterations, all of which shape prognosis and treatment outcomes. While some variants correlate with immune infiltration and better survival, others, especially when co-mutated, predict aggressive disease and poor outcomes. Furthermore, FBXW7 alterations contribute to chemoresistance and anti-EGFR therapy resistance but also reveal potential therapeutic vulnerabilities. These findings underscore FBXW7\u2019s promise as a prognostic biomarker and a potential target for precision oncology strategies in colorectal cancer.<\/jats:p>","DOI":"10.3390\/ijms262311318","type":"journal-article","created":{"date-parts":[[2025,11,24]],"date-time":"2025-11-24T09:02:07Z","timestamp":1763974927000},"page":"11318","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["FBXW7 Gene Mutation and Expression in Colorectal Cancer (CRC): A Systematic Review from Molecular Mechanisms to Clinical Translation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0541-415X","authenticated-orcid":false,"given":"Giulia","family":"Arrivi","sequence":"first","affiliation":[{"name":"Oncology Unit, Department of Clinical and Molecular Medicine, Sant\u2019Andrea University Hospital, Sapienza University of Rome, 00189 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-2714-2769","authenticated-orcid":false,"given":"Gabriella","family":"Gentile","sequence":"additional","affiliation":[{"name":"Department of Experimental Medicine, Sapienza University of Rome, Viale Regina Elena, 324, 00161 Rome, Italy"},{"name":"Department of Radiological, Oncological and Pathological Science, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5339-8348","authenticated-orcid":false,"given":"Michela","family":"Roberto","sequence":"additional","affiliation":[{"name":"Oncology Unit, Policlinico Umberto I, Haematological, Oncological and Dermatological Department, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donatella","family":"Delle Cave","sequence":"additional","affiliation":[{"name":"Institute of Genetics and Biophysics \u2018Adriano Buzzati-Traverso\u2019 (IGB), National Research Council (CNR), 80131 Naples, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1038\/nature09796","article-title":"A decade\u2019s perspective on DNA sequencing technology","volume":"470","author":"Mardis","year":"2011","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1083\/jcb.201612010","article-title":"Why proteomics is not the new genomics and the future of mass spectrometry in cell biology","volume":"216","author":"Sidoli","year":"2017","journal-title":"J. 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