PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established patient-derived cell panel assay
PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established patient-derived cell panel assay
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使用新建立的源自患者的细胞组检测将 PI3K-mTOR 通路确定为胆道癌的潜在治疗靶点
DOI：
10.1093/jjco/hyy011
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发表时间：
2018
影响因子：
2.4
通讯作者：
Ojima H
中科院分区：
文献类型：
--
作者：
Sakamoto Y.;Yamagishi S.;Tanizawa Y.;Tajimi M.;Okusaka T.;Ojima H
胆道癌是一种恶性程度极高的肿瘤，但治疗方法有限。尽管需要新的治疗方法，但目前很少有BTC相关资源可用于评估候选药物。为了解决这个问题，我们最近从日本BTC患者的手术标本中建立了13个细胞系。在本研究中，我们使用我们的基于BTC细胞的测定面板与17个BTC细胞系评估了四种新的分子靶向剂。PI 3 K/mTOR双重抑制剂LY 3023414在亚微摩尔浓度范围内显示出对17种测试细胞系中的13种的活性，包括具有吉西他滨不敏感性的细胞系。总之，我们证明了BTC细胞系组的体外研究将是筛选新治疗策略的有效方法。虽然这是初步结果，还需要进一步的研究来证实，但PI 3 K/mTOR抑制剂可能是BTC药物开发的潜在靶点。
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 thatin vitrostudy 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.