Olaparib in treatment-refractory isocitrate dehydrogenase 1 (IDH1)- and IDH2-mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial.

doi:10.1002/cncr.35755

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Article

Olaparib in treatment-refractory isocitrate dehydrogenase 1 (IDH1)- and IDH2-mutant cholangiocarcinoma: Safety and antitumor activity from the phase 2 National Cancer Institute 10129 trial.

Cancer - 15 Feb 2025

Cecchini Michael, Pilat Mary Jo, Uboha Nataliya, Azad Nilofer S, Cho May, Davis Elizabeth J, Ahnert Jordi Rodon, Tinoco Gabriel, Shapiro Geoffrey I, Khagi Simon, Powers Benjamin, Spencer Kristen, Groisberg Roman, Drappatz Jan, Chen Li, Das Biswajit, Bao Xun, Li Jing, Narayan Azeet, Vu Dennis, Patel Abhijit, Niger Monica, Doroshow Deborah, Durecki Diane, Boerner Scott A, Bindra Ranjit, Ivy Percy, Shyr Derek, Shyr Yu, LoRusso Patricia M

Abstract excerpt

BACKGROUND: Neomorphic isocitrate dehydrogenase (IDH) mutations lead to the accumulation of 2-hydroxyglutarate (2-HG), an oncometabolite implicated in tumor progression via inhibitory effects on alpha-ketoglutarate. Moreover, mutant IDH-dependent accumulation of 2-HG results in homologous recombination deficiency (HRD), which preclinically renders tumors sensitive to poly(adenosine diphosphate ribose) polymerase...

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PMID: 39917990
DOI: 10.1002/cncr.35755
PMCID: PMC11949439

Genes

IDH1
IDH2

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