{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:53:41Z","timestamp":1790916821742,"version":"4.1.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Associations between genetically predicted activity of metabolic enzymes and risks of adverse events from tyrosine kinase inhibitors (TKIs) may inform dosing to optimize treatment outcomes in patients with cancer. The goal of this study is to investigate the associations between UGT1A1, CYP3A4, and CYP1A2 activity and toxicity from nilotinib and pazopanib treatment. A retrospective pharmacogenetic association study was conducted in 117 participants of the Michigan Genomics Initiative who received pazopanib (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2005=\u2005103) or nilotinib (\n                      <jats:italic toggle=\"yes\">n<\/jats:italic>\n                      \u2005=\u200514). Clinical information, including patients\u2019 disease, treatment, and toxicity was collected via retrospective review of medical records. No associations were found between the genetically predicted activity of any of the three enzymes and the composite endpoint of severe toxicity or treatment modifications because of toxicity. In the secondary hypothesis-generating analyses, patients with reduced UGT1A1 activity had an increased incidence of increased aspartate aminotransferase\/alanine aminotransferase (44 vs. 25%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005=\u20050.034) and hypertension (52 vs. 31%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005=\u20050.024). In addition, patients with increased CYP1A2 activity from carrying\n                      <jats:italic toggle=\"yes\">CYP1A2*1F<\/jats:italic>\n                      had a lower incidence of severe toxicity from pazopanib (\n                      <jats:italic toggle=\"yes\">\u03b2<\/jats:italic>\n                      -coefficient = \u20100.163, 95% confidence interval: \u20100.19 to \u20100.14,\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      \u2005=\u20050.008). Future investigations are needed to confirm these associations and determine whether personalized TKI treatment can optimize therapeutic outcomes in patients with cancer.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1097\/fpc.0000000000000613","type":"journal-article","created":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T05:00:06Z","timestamp":1785646806000},"page":"295-300","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":0,"title":["Association of UGT and CYP genotype-predicted activity with tyrosine kinase inhibitor toxicity"],"prefix":"10.1097","volume":"36","author":[{"given":"April T.","family":"Moy","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia E.","family":"D\u2019Angelo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel L.","family":"Hertz","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, University of Michigan College of Pharmacy, Ann Arbor, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"R3-20261002","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.3390\/cancers13071566","article-title":"UGT1A1 guided cancer therapy: review of the evidence and considerations for clinical implementation.","volume":"13","author":"Nelson","year":"2021","journal-title":"Cancers (Basel)"},{"key":"R4-20261002","doi-asserted-by":"crossref","first-page":"2927","DOI":"10.1093\/annonc\/mdt394","article-title":"Hyperbilirubinemia in pazopanib- or sunitinib-treated patients in COMPARZ is associated with UGT1A1 polymorphisms.","volume":"24","author":"Motzer","year":"2013","journal-title":"Ann Oncol"},{"key":"R5-20261002","doi-asserted-by":"crossref","first-page":"449","DOI":"10.2133\/dmpk.DMPK-14-RG-031","article-title":"Influence of UGT1A1 6, 27, and 28 polymorphisms on nilotinib-induced hyperbilirubinemia in Japanese patients with chronic myeloid leukemia.","volume":"29","author":"Abumiya","year":"2014","journal-title":"Drug Metab Pharmacokinet"},{"key":"R6-20261002","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1177\/0091270010367428","article-title":"Effects of rifampin and ketoconazole on the pharmacokinetics of nilotinib in healthy participants.","volume":"51","author":"Tanaka","year":"2011","journal-title":"J Clin Pharmacol"},{"key":"R7-20261002","doi-asserted-by":"crossref","first-page":"1635","DOI":"10.1007\/s00280-013-2164-3","article-title":"Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors.","volume":"71","author":"Tan","year":"2013","journal-title":"Cancer Chemother Pharmacol"},{"key":"R8-20261002","doi-asserted-by":"crossref","first-page":"473","DOI":"10.1038\/s41397-019-0079-z","article-title":"Genetic polymorphisms in ABCG2 and CYP1A2 are associated with imatinib dose reduction in patients treated for gastrointestinal stromal tumors.","volume":"19","author":"Verboom","year":"2019","journal-title":"Pharmacogenomics J"},{"key":"R9-20261002","doi-asserted-by":"crossref","first-page":"100257","DOI":"10.1016\/j.xgen.2023.100257","article-title":"The Michigan Genomics Initiative: a biobank linking genotypes and electronic clinical records in Michigan Medicine patients.","volume":"3","author":"Zawistowski","year":"2023","journal-title":"Cell Genom"},{"key":"R10-20261002","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1002\/cpt.1568","article-title":"Pharmacogenomics Clinical Annotation Tool (PharmCAT).","volume":"107","author":"Sangkuhl","year":"2020","journal-title":"Clin Pharmacol Ther"},{"key":"R11-20261002","doi-asserted-by":"crossref","first-page":"2082","DOI":"10.3390\/pharmaceutics14102082","article-title":"Genotyping of UGT1A1*80 as an Alternative to UGT1A1*28 Genotyping in Spain.","volume":"14","author":"Bravo-G\u00f3mez","year":"2022","journal-title":"Pharmaceutics"},{"key":"R12-20261002","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1097\/FPC.0b013e328014341f","article-title":"Irinotecan pharmacokinetics\/pharmacodynamics and UGT1A genetic polymorphisms in Japanese: roles of UGT1A1*6 and *28.","volume":"17","author":"Minami","year":"2007","journal-title":"Pharmacogenet Genomics"},{"key":"R13-20261002","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1038\/sj.tpj.6500072","article-title":"UGT1A1*28 polymorphism as a determinant of irinotecan disposition and toxicity.","volume":"2","author":"Iyer","year":"2002","journal-title":"Pharmacogenomics J"},{"key":"R14-20261002","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1007\/s40262-018-0719-5","article-title":"Impact of CYP3A4*22 on pazopanib pharmacokinetics in cancer patients.","volume":"58","author":"Bins","year":"2019","journal-title":"Clin Pharmacokinet"},{"key":"R15-20261002","doi-asserted-by":"crossref","first-page":"109700","DOI":"10.1016\/j.cbi.2021.109700","article-title":"Functional evaluation of vandetanib metabolism by CYP3A4 variants and potential drug interactions in vitro.","volume":"350","author":"Han","year":"2021","journal-title":"Chem Biol Interact"},{"key":"R16-20261002","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/cts.12598","article-title":"Effects of common CYP1A2 genotypes and other key factors on intraindividual variation in the caffeine metabolic ratio: an exploratory 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the use of weak CYP3A4 and P-gp inhibitors.","volume":"76","author":"Azam","year":"2020","journal-title":"Eur J Clin Pharmacol"}],"container-title":["Pharmacogenetics and 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History"}},{"value":"2026-06-12","name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}}]}}