Preferential effect of PARP-1 inhibition in KRAS-mutated intrahepatic cholangiocarcinomas is mediated by CHK1/2 kinases

Darko Castven,Friederike Keggenhoff, Stojan Stojkovic,Diana Becker, Jovana Castven,Carolin Zimpel, BeateKatharina Straub,Harald F. Langer,Patricia S. Hähnel,Thomas Kindler,Jörg Fahrer, ColmJ. O’Rourke,Lichun Ma, XinW. Wang,Timo Gaiser, MatthiasS. Matter, Christian Sina, Stefanie Derer, Stephanie Rössler,Bernd Kaina, JesperB. Andersen, P Galle, J. Marquardt

Zeitschrift Fur Gastroenterologie（2023）

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摘要

Activating KRAS mutations are among the most abundant genetic alterations in intrahepatic cholangiocarcinoma (iCCA) and are associated with early recurrence, poor response, and reduced survival. Poly(ADP-ribose)polymerase-1 (PARP-1) is frequently observed to be upregulated in iCCA. Evidence indicate potential therapeutic relevance for PARP-1 inhibition in iCCA that preferentially affects KRAS-mutated cancers, but exact mechanisms remain unknown.

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关键词

intrahepatic cholangiocarcinomas,kras-mutated

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