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mTOR Inhibitors in Advanced Biliary Tract Cancers
Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386826/ https://www.ncbi.nlm.nih.gov/pubmed/30682771 http://dx.doi.org/10.3390/ijms20030500 |
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author | Wu, Chao-En Chen, Ming-Huang Yeh, Chun-Nan |
author_facet | Wu, Chao-En Chen, Ming-Huang Yeh, Chun-Nan |
author_sort | Wu, Chao-En |
collection | PubMed |
description | Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of mTOR inhibitors as a future treatment in BTC. Chemotherapy with gemcitabine-based chemotherapy is still the standard of care and no targeted therapy has been established in advanced BTC. PI3K/AKT/mTOR signaling pathway linking to several other pathways and networks regulates cancer proliferation and progression. Emerging evidences reveal mTOR activation is associated with tumorigenesis and drug-resistance in BTC. Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Rapalogs in clinical trials demonstrate some activity in patients with advanced BTC. New-generation mTOR inhibitors against ATP-binding pocket inhibit both TORC1 and TORC2 and demonstrate more potent anti-tumor effects in vitro and in vivo, however, prospective clinical trials are warranted to prove its efficacy in patients with advanced BTC. |
format | Online Article Text |
id | pubmed-6386826 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-63868262019-02-27 mTOR Inhibitors in Advanced Biliary Tract Cancers Wu, Chao-En Chen, Ming-Huang Yeh, Chun-Nan Int J Mol Sci Review Patients with advanced biliary tract cancers (BTCs), including cholangiocarcinoma (CCA), have poor prognosis so novel treatment is warranted for advanced BTC. In current review, we discuss the limitations of current treatment in BTC, the importance of mTOR signalling in BTC, and the possible role of mTOR inhibitors as a future treatment in BTC. Chemotherapy with gemcitabine-based chemotherapy is still the standard of care and no targeted therapy has been established in advanced BTC. PI3K/AKT/mTOR signaling pathway linking to several other pathways and networks regulates cancer proliferation and progression. Emerging evidences reveal mTOR activation is associated with tumorigenesis and drug-resistance in BTC. Rapalogs, such as sirolimus and everolimus, partially inhibit mTOR complex 1 (mTORC1) and exhibit anti-cancer activity in vitro and in vivo in BTC. Rapalogs in clinical trials demonstrate some activity in patients with advanced BTC. New-generation mTOR inhibitors against ATP-binding pocket inhibit both TORC1 and TORC2 and demonstrate more potent anti-tumor effects in vitro and in vivo, however, prospective clinical trials are warranted to prove its efficacy in patients with advanced BTC. MDPI 2019-01-24 /pmc/articles/PMC6386826/ /pubmed/30682771 http://dx.doi.org/10.3390/ijms20030500 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Wu, Chao-En Chen, Ming-Huang Yeh, Chun-Nan mTOR Inhibitors in Advanced Biliary Tract Cancers |
title | mTOR Inhibitors in Advanced Biliary Tract Cancers |
title_full | mTOR Inhibitors in Advanced Biliary Tract Cancers |
title_fullStr | mTOR Inhibitors in Advanced Biliary Tract Cancers |
title_full_unstemmed | mTOR Inhibitors in Advanced Biliary Tract Cancers |
title_short | mTOR Inhibitors in Advanced Biliary Tract Cancers |
title_sort | mtor inhibitors in advanced biliary tract cancers |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386826/ https://www.ncbi.nlm.nih.gov/pubmed/30682771 http://dx.doi.org/10.3390/ijms20030500 |
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