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

Yasunari Sakamoto; Seri Yamagishi; Yoshinori Tanizawa; Masaomi Tajimi; Takuji Okusaka; Hidenori Ojima

doi:10.1093/jjco/hyy011

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

Yasunari Sakamoto, Seri Yamagishi, Yoshinori Tanizawa, Masaomi Tajimi, Takuji Okusaka, Hidenori Ojima

Department of Pathology

Research output: Contribution to journal › Article › peer-review

8 Citations (Scopus)

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.

Original language	English
Pages (from-to)	396-399
Number of pages	4
Journal	Japanese journal of clinical oncology
Volume	48
Issue number	4
DOIs	https://doi.org/10.1093/jjco/hyy011
Publication status	Published - 2018 Apr 1

Keywords

Antitumor
Biliary tract cancer
Drug resistance
Drug screening assays
Neoplasm
Phosphatidylinositol 3-kinases
Serine-threonine kinases
TOR

ASJC Scopus subject areas

Oncology
Radiology Nuclear Medicine and imaging
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/jjco/hyy011

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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. / Sakamoto, Yasunari; Yamagishi, Seri; Tanizawa, Yoshinori; Tajimi, Masaomi; Okusaka, Takuji; Ojima, Hidenori.

In: Japanese journal of clinical oncology, Vol. 48, No. 4, 01.04.2018, p. 396-399.

Research output: Contribution to journal › Article › peer-review

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

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.",

keywords = "Antitumor, Biliary tract cancer, Drug resistance, Drug screening assays, Neoplasm, Phosphatidylinositol 3-kinases, Serine-threonine kinases, TOR",

author = "Yasunari Sakamoto and Seri Yamagishi and Yoshinori Tanizawa and Masaomi Tajimi and Takuji Okusaka and Hidenori Ojima",

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AU - Sakamoto, Yasunari

AU - Yamagishi, Seri

AU - Tanizawa, Yoshinori

AU - Tajimi, Masaomi

AU - Okusaka, Takuji

AU - Ojima, Hidenori

PY - 2018/4/1

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N2 - 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.

AB - 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.

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KW - Biliary tract cancer

KW - Drug resistance

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KW - Neoplasm

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KW - Serine-threonine kinases

KW - TOR

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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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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