{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T04:59:08Z","timestamp":1785473948306,"version":"3.56.0"},"reference-count":96,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Gilead Sciences","award":["0389767"],"award-info":[{"award-number":["0389767"]}]},{"award":["0389767"],"award-info":[{"award-number":["0389767"]}],"id":[{"id":"https:\/\/ror.org\/056546b03","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Pharmacogenetics has transformed oncology by enabling personalized, effective and safer use of anticancer therapies. Among clinically relevant pharmacogenetic biomarkers, polymorphisms in the UGT1A1 gene influence the metabolism of irinotecan and other SN-38-based agents, increasing the risk of treatment-related toxicities. Beyond SN-38-based therapies, UGT1A1 contributes to the metabolism of endogenous compounds and several drugs, and its activity may be affected by concomitant inhibitors or inducers, highlighting its broader clinical relevance. Although substantial evidence supports the association between UGT1A1 genotype and drug safety, implementation of genotype-guided treatment remains inconsistent. This narrative review summarizes the biological basis and clinical relevance of UGT1A1 polymorphisms in patients receiving SN-38-based therapies. Original studies, systematic reviews, meta-analyses, and international and regional pharmacogenetic guidelines were evaluated regarding genotype-guided dosing, clinical outcomes, implementation strategies, and barriers to routine testing. Reduced-function UGT1A1 variants are associated with increased risk of irinotecan-induced neutropenia and diarrhea, particularly at higher doses. However, recommendations from scientific societies differ regarding testing indications, dose adjustment strategies, and patient selection. Uncertainties remain concerning the clinical implications of UGT1A1 variability for newer antibody\u2013drug conjugates carrying an SN-38 payload. Practical barriers, including inconsistent guideline recommendations, limited access to testing, reimbursement issues, and heterogeneous clinical workflows, continue to restrict implementation. UGT1A1 genotyping represents a valuable tool for improving the safety of selected anticancer therapies, yet its incorporation into clinical practice remains incomplete. As precision oncology evolves, pharmacogenetic testing may optimize treatment selection, reduce toxicity, and improve outcomes. Further harmonization of international recommendations, high-quality prospective studies, and wider access to pharmacogenetic testing are needed to support routine implementation.<\/jats:p>","DOI":"10.3390\/pharmaceutics18080928","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T10:13:47Z","timestamp":1785320027000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Implications of UGT1A1 Polymorphisms in Anticancer Therapy: An Updated Review"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7948-3580","authenticated-orcid":false,"given":"Silvia R.","family":"Vitale","sequence":"first","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"Drago","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-2914","authenticated-orcid":false,"given":"Federica","family":"Martorana","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Humanitas Istituto Clinico Catanese, Misterbianco, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-7219-2477","authenticated-orcid":false,"given":"Chiara","family":"Conti","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5896-8573","authenticated-orcid":false,"given":"Michele","family":"Massimino","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of General Surgery and Medical-Surgical Sciences, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Stella","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1044-1008","authenticated-orcid":false,"given":"Cristina","family":"Tomarchio","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Vigneri","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"},{"name":"Humanitas Istituto Clinico Catanese, Misterbianco, 95125 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Manzella","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology and Hematology, A.O.U. Policlinico \u201cG. Rodolico-S. Marco\u201d, 95123 Catania, Italy"},{"name":"Department of Clinical and Experimental Medicine, University of Catania, 95123 Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.ccell.2021.12.004","article-title":"Functional precision oncology: Testing tumors with drugs to identify vulnerabilities and novel combinations","volume":"40","author":"Letai","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"100629","DOI":"10.1016\/j.esmoop.2022.100629","article-title":"Health-related quality of life in breast cancer patients treated with CDK4\/6 inhibitors: A systematic review","volume":"7","author":"Barchiesi","year":"2022","journal-title":"ESMO Open"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/S0140-6736(19)31276-0","article-title":"Pharmacogenomics","volume":"394","author":"Roden","year":"2019","journal-title":"Lancet"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.annonc.2022.10.003","article-title":"Metastatic colorectal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up","volume":"34","author":"Cervantes","year":"2023","journal-title":"Ann. 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