Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models

Abstract When breast cancer patients start to exhibit resistance to hormonal therapy or chemotherapy, the mTOR inhibitor everolimus can be considered as an alternative therapeutic agent. Everolimus can deregulate the PI3K/AKT/mTOR pathway and affect a range of cellular functions. In some patients, t...

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Autores principales:	Chun-Ting Kuo, Chen-Lin Chen, Chih-Chi Li, Guan-Syuan Huang, Wei-Yuan Ma, Wei-Fan Hsu, Ching-Hung Lin, Yen-Shen Lu, Andrew M. Wo
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c7eb9d6b994340dfae24eaf48c223d35
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spelling	oai:doaj.org-article:c7eb9d6b994340dfae24eaf48c223d352021-12-02T15:10:02ZImmunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models10.1038/s41598-019-45319-42045-2322https://doaj.org/article/c7eb9d6b994340dfae24eaf48c223d352019-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-45319-4https://doaj.org/toc/2045-2322Abstract When breast cancer patients start to exhibit resistance to hormonal therapy or chemotherapy, the mTOR inhibitor everolimus can be considered as an alternative therapeutic agent. Everolimus can deregulate the PI3K/AKT/mTOR pathway and affect a range of cellular functions. In some patients, the agent does not exhibit the desired efficacy and, even worse, not without the associated side effects. This study assessed the use of immunofluorescence (IF) as a modality to fill this unmet need of predicting the efficacy of everolimus prior to administration. Cell viability and MTT assays based on IF intensities of pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 on breast cancer cells (Hs578T, MCF7, BT474, MDA-MB-231) and patient-derived cell culture from metastatic sites (ABC-82T and ABC-16TX1) were interrogated. Results show that independent pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 IF expressions can classify data into different groups: everolimus sensitive and resistant. The combined IF baseline intensity of these proteins is predictive of the efficacy of everolimus, and their intensities change dynamically when cells are resistant to everolimus. Furthermore, mTOR resistance is not only consequence of the AKT/mTOR pathway but also through the LKB1 or MAPK/ERK pathway. The LKB1 and pho-GSK3β may also be potential predictive markers for everolimus.Chun-Ting KuoChen-Lin ChenChih-Chi LiGuan-Syuan HuangWei-Yuan MaWei-Fan HsuChing-Hung LinYen-Shen LuAndrew M. WoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-11 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Chun-Ting Kuo Chen-Lin Chen Chih-Chi Li Guan-Syuan Huang Wei-Yuan Ma Wei-Fan Hsu Ching-Hung Lin Yen-Shen Lu Andrew M. Wo Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
description	Abstract When breast cancer patients start to exhibit resistance to hormonal therapy or chemotherapy, the mTOR inhibitor everolimus can be considered as an alternative therapeutic agent. Everolimus can deregulate the PI3K/AKT/mTOR pathway and affect a range of cellular functions. In some patients, the agent does not exhibit the desired efficacy and, even worse, not without the associated side effects. This study assessed the use of immunofluorescence (IF) as a modality to fill this unmet need of predicting the efficacy of everolimus prior to administration. Cell viability and MTT assays based on IF intensities of pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 on breast cancer cells (Hs578T, MCF7, BT474, MDA-MB-231) and patient-derived cell culture from metastatic sites (ABC-82T and ABC-16TX1) were interrogated. Results show that independent pho-4EBP1 Thr37/46 and pho-S6K1 Ser424 IF expressions can classify data into different groups: everolimus sensitive and resistant. The combined IF baseline intensity of these proteins is predictive of the efficacy of everolimus, and their intensities change dynamically when cells are resistant to everolimus. Furthermore, mTOR resistance is not only consequence of the AKT/mTOR pathway but also through the LKB1 or MAPK/ERK pathway. The LKB1 and pho-GSK3β may also be potential predictive markers for everolimus.
format	article
author	Chun-Ting Kuo Chen-Lin Chen Chih-Chi Li Guan-Syuan Huang Wei-Yuan Ma Wei-Fan Hsu Ching-Hung Lin Yen-Shen Lu Andrew M. Wo
author_facet	Chun-Ting Kuo Chen-Lin Chen Chih-Chi Li Guan-Syuan Huang Wei-Yuan Ma Wei-Fan Hsu Ching-Hung Lin Yen-Shen Lu Andrew M. Wo
author_sort	Chun-Ting Kuo
title	Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
title_short	Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
title_full	Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
title_fullStr	Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
title_full_unstemmed	Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models
title_sort	immunofluorescence can assess the efficacy of mtor pathway therapeutic agent everolimus in breast cancer models
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/c7eb9d6b994340dfae24eaf48c223d35
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Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models

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