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

Japanese Journal of Clinical Oncology
Yasunari SakamotoHidenori Ojima

Abstract

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.

References

Apr 9, 2010·The New England Journal of Medicine·Juan ValleUNKNOWN ABC-02 Trial Investigators
Jul 9, 2013·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Supak YothaisongWatcharin Loilome
Apr 24, 2014·Japanese Journal of Clinical Oncology·Hiroyuki TakahashiTatsuhiro Shibata
Aug 11, 2015·Nature Genetics·Hiromi NakamuraTatsuhiro Shibata
Jun 12, 2016·Pharmacology & Therapeutics·Beverly L FalconBronislaw Pytowski
Nov 12, 2016·World Journal of Gastroenterology : WJG·Hidenori OjimaTatsuhiro Shibata

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Citations

Aug 23, 2020·Surgical Oncology·Amir A Rahnemai-AzarTimothy M Pawlik
Mar 5, 2021·OncoTargets and Therapy·Wenwei Yang, Yongkun Sun

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