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PI3K-mTOR pathway identified as a potential therapeutic target in biliary tract cancer using a newly established

Yasunari Sakamoto1, Seri Yamagishi2, Yoshinori Tanizawa3

  • 1Department of Hepatobiliary and Pancreatic Oncology, Tokyo, National Cancer Center Hospital.

Japanese Journal of Clinical Oncology
|February 24, 2018
PubMed

Insights

Novel therapies for biliary tract carcinoma (BTC) are needed. A PI3K/mTOR dual inhibitor demonstrated significant activity against 13 of 17 BTC cell lines, suggesting its potential for drug development.

Area of Science:

  • Oncology
  • Drug Discovery
  • Gastroenterology

Background:

  • Biliary tract carcinoma (BTC) is a highly malignant cancer with limited treatment options.
  • There is a critical need for novel therapeutic strategies and accessible resources for drug evaluation in BTC.
  • Existing BTC models are insufficient for comprehensive preclinical drug screening.

Purpose of the Study:

  • To establish and utilize a panel of Japanese biliary tract carcinoma cell lines for drug screening.
  • To evaluate the efficacy of four novel molecular targeting agents against BTC.
  • To identify promising therapeutic targets for biliary tract carcinoma.

Main Methods:

  • Establishment of 13 new cell lines from surgical specimens of Japanese BTC patients.
  • In vitro evaluation of four molecular targeting agents using a panel of 17 BTC cell lines.
  • Assessment of drug activity at submicromolar concentration ranges.

Main Results:

  • The PI3K/mTOR dual inhibitor LY3023414 exhibited potent activity against 13 out of 17 BTC cell lines.
  • Activity was observed even in cell lines resistant to gemcitabine.
  • The BTC cell line panel proved effective for screening novel therapeutic agents.

Conclusions:

  • An in vitro study using a biliary tract carcinoma cell line panel is an efficient method for screening novel therapeutic strategies.
  • PI3K/mTOR dual inhibitors represent a potential therapeutic target for biliary tract carcinoma drug development.
  • Further investigation is warranted to confirm these preliminary findings.

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