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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 (  IDH 1/2 ) are exclusively found in almost 20% of intrahepatic cholangiocarcinoma ( ICC ). Recently, the anticancer effects of  BET  inhibitors including  JQ 1 have been shown in various tumors. In the present study, we report that the antigrowth effect of  JQ 1 differs among  ICC  cells and   IDH 1  mutation sensitizes  ICC  cells to  JQ 1.  RBE  cells harboring   IDH 1  mutation was more sensitive to  JQ 1 than Hu CCT 1 or HuH28 cells with wild‐type   IDH 1 .  JQ 1 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  JQ 1 in various cancer cells. Notably, the forced expression of mutant  IDH 1 successfully sensitized Hu CCT 1 cells to  JQ 1. In addition,  AGI ‐5198, a selective inhibitor of mutant  IDH 1 partially reversed the decrease in viability after  JQ 1 treatment and also suppressed the  JQ 1‐induced apoptosis in  RBE  cells. These data suggest that   IDH 1  mutation contributed to the growth inhibitory effect of  JQ 1 in  RBE  cells. Furthermore, given that the effect of mutant  IDH 1 was not recapitulated in glioblastoma cells, the enhancement of  JQ 1 sensitivity by   IDH 1  mutation seems to be specific for  ICC  cells. Our findings propose a new stratified therapeutic strategy based on   IDH 1  mutation in  ICC .

Isocitrate dehydrogenase 1 mutation sensitizes intrahepatic cholangiocarcinoma to the BET inhibitor JQ 1