ArticleCancer science2018
Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ1.
Article in Cancer science, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 17 citations in OpenAlex.
- Low expression of RACK1 is associated with metastasis and worse prognosis in cholangiocarcinoma.Heliyon · 2024Article
- CRISPR screening identifies BET and mTOR inhibitor synergy in cholangiocarcinoma through serine glycine one carbon.JCI insight · 2024Article
- Review
- Human Metastatic Cholangiocarcinoma Patient-Derived Xenografts and Tumoroids for Preclinical Drug Evaluation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- R132H IDH1 sensitizes glioma to the antiproliferative and cytotoxic effects of BET inhibition.Journal of cancer research and clinical oncology · 2022Article
- Selecting an Appropriate Experimental Animal Model for Cholangiocarcinoma Research.Journal of clinical and translational hepatology · 2022Review
- BRD4: An emerging prospective therapeutic target in glioma.Molecular therapy oncolytics · 2021Review
- Small molecules in targeted cancer therapy: advances, challenges, and future perspectives.Signal transduction and targeted therapy · 2021Review
- Review
- Identification of Circulating Genomic and Metabolic Biomarkers in Intrahepatic Cholangiocarcinoma.Cancers · 2019Article
- Distinct histomorphological features are associated with IDH1 mutation in intrahepatic cholangiocarcinoma.Human pathology · 2019Article
- BRD4 degrader ARV-825 produces long-lasting loss of BRD4 protein and exhibits potent efficacy against cholangiocarcinoma cells.American journal of translational research · 2019Article
- Mutant Isocitrate Dehydrogenase Inhibitors as Targeted Cancer Therapeutics.Frontiers in oncology · 2019Review
- Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ1.Cancer science · 2018Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Cholangiocarcinoma is a life-threatening disease with a poor prognosis. Although genome analysis unraveled some genetic mutation profiles in cholangiocarcinoma, it remains unknown whether such genetic abnormalities relate to the effects of anticancer drugs. Mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma (ICC). Recently, the anticancer effects of BET inhibitors including JQ1 have been shown in various tumors. In the present study, we report that the antigrowth effect of JQ1 differs among ICC cells and IDH1 mutation sensitizes ICC cells to JQ1. RBE cells harboring IDH1 mutation was more sensitive to JQ1 than HuCCT1 or HuH28 cells with wild-type IDH1. JQ1 induced apoptosis only in RBE cells through the upregulation of proapoptotic genes BAX and BIM. We found that the antigrowth effect was not attributed to downregulation of the MYC gene as a well-known target of JQ1 in various cancer cells. Notably, the forced expression of mutant IDH1 successfully sensitized HuCCT1 cells to JQ1. In addition, AGI-5198, a selective inhibitor of mutant IDH1 partially reversed the decrease in viability after JQ1 treatment and also suppressed the JQ1-induced apoptosis in RBE cells. These data suggest that IDH1 mutation contributed to the growth inhibitory effect of JQ1 in RBE cells. Furthermore, given that the effect of mutant IDH1 was not recapitulated in glioblastoma cells, the enhancement of JQ1 sensitivity by IDH1 mutation seems to be specific for ICC cells. Our findings propose a new stratified therapeutic strategy based on IDH1 mutation in ICC.
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