{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T18:13:38Z","timestamp":1792088018645,"version":"4.4.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T00:00:00Z","timestamp":1721606400000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100017065","name":"Rogel Cancer Center, University of Michigan","doi-asserted-by":"publisher","award":["P30CA046592"],"award-info":[{"award-number":["P30CA046592"]}],"id":[{"id":"10.13039\/100017065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,8,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Isocitrate dehydrogenase 1 (IDH1) missense mutations occur at a frequency of 10%-15% in intrahepatic cholangiocarcinoma (iCCA). IDH1 mutations result in accumulation of (R)-2-hydroxyglutarate, an oncometabolite that leads to DNA hypermethylation and impairment of homologous recombination (HR). Impairment of HR results in a \u201cBRCAness\u201d phenotype which may confer sensitivity to poly(ADP ribose) polymerase (PARP) inhibition.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We conducted a retrospective cohort review to identify patients with advanced, IDH1 mutated iCCA treated with a PARP inhibitor (PARPi) at the University of Michigan between 2018 and 2023. Patients are described with respect to prior lines of therapy, response to platinum-based chemotherapy, and progression-free survival (PFS) and overall survival (OS) from the time of PARPi initiation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Between 2018 and 2023 we identified 40 patients with IDH1 mutated iCCA of which 6 patients were treated with a PARPi as monotherapy or in combination with an ATR inhibitor or anti-PD-1 immune checkpoint inhibitor. Majority of patients (n\u2005=\u20055) carried an IDH1 R132C mutation per tissue-based next generation sequencing. All patients had previously received at least one line of cisplatin-based systemic therapy for advanced disease prior to treatment with PARPi. PFS and OS from time of PARPi initiation ranged from 1.4 to 18.5 months and 2.8 to 42.4 months, respectively. Best response on PARPi therapy included 2 partial responses.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>This is the first case series to describe PARPi treatment in IDH1 mutated iCCA. Results underscore the limitation of PARPi monotherapy, potentially support combined PARPi therapies, and highlight a need for effective treatment options for patients with IDH1 mutated iCCA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyae163","type":"journal-article","created":{"date-parts":[[2024,7,22]],"date-time":"2024-07-22T10:36:09Z","timestamp":1721644569000},"page":"725-730","source":"Crossref","is-referenced-by-count":13,"title":["PARP inhibitor therapy in patients with <i>IDH1<\/i> mutated cholangiocarcinoma"],"prefix":"10.1093","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9024-6589","authenticated-orcid":false,"given":"Arathi","family":"Mohan","sequence":"first","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI , United States"},{"name":"Rogel Cancer Center, University of Michigan , Ann Arbor, MI , United 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University of Michigan , Ann Arbor, MI , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vaibhav","family":"Sahai","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan , Ann Arbor, MI , United States"},{"name":"Rogel Cancer Center, University of Michigan , Ann Arbor, MI , United States"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,7,20]]},"reference":[{"issue":"4","key":"2024080521125978700_CIT0001","doi-asserted-by":"crossref","first-page":"652","DOI":"10.21037\/jgo.2018.08.18","article-title":"Molecular profiling of biliary cancers reveals distinct molecular alterations and potential therapeutic targets","volume":"10","author":"Weinberg","year":"2019","journal-title":"J Gastrointest 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