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PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established patient-derived cell panel assay

机译:使用新建立的患者衍生的细胞面板测定鉴定为胆囊癌的潜在治疗靶标的PI3K-MTOR途径

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摘要

Biliary tract carcinoma (BTC) is an extremely malignant tumor, but available treatment options are limited. Despite of needs for novel therapies, few BTC-related resources are currently available for evaluation of candidate drugs. To address this issue, we have recently established 13 cell lines from surgical specimens from Japanese BTC patients. In the present study, we evaluated four new molecular targeting agents using our BTC cell-based assay panel with 17 BTC cell lines. PI3K/mTOR dual inhibitor LY3023414 showed activity at submicromolar concentration ranges against 13 of the 17 cell lines tested, including the ones with gemcitabine insensitivity. In conclusion, we demonstrated that in vitro study with the BTC cell line panel would be an efficient approach to screen for novel therapeutic strategies. Although this is preliminary result and further investigations are required for confirmation, PI3K/mTOR inhibitor might be a potential target for BTC drug development.
机译:胆管癌(BTC)是一种极其恶性肿瘤,但可用的治疗方案有限。 尽管需要进行小说疗法,但目前有很少的BTC相关资源可用于评估候选药物。 为解决这个问题,我们最近从日本BTC患者的手术标本中建立了13条细胞系。 在本研究中,我们使用具有17个BTC细胞系的BTC细胞基测定面板评估了四种新的分子靶向剂。 PI3K / mTOR双抑制剂LY3023414显示亚微粒粒子浓度范围的活性与测试的17条细胞系中的13条,包括具有吉西他滨的细胞的细胞。 总之,我们证明,与BTC细胞系面板的体外研究将是筛选新的治疗策略的有效方法。 虽然这是初步结果,但确认需要进一步的研究,PI3K / mTOR抑制剂可能是BTC药物发育的潜在目标。

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