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Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells

Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benef...

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Autores principales: Naka, Kazuhito, Ishihara, Kaori, Jomen, Yoshie, Jin, Cheng Hua, Kim, Dong‐Hyun, Gu, Yoon‐Kang, Jeong, Eun‐Sook, Li, Shaoguang, Krause, Daniela S., Kim, Dong‐Wook, Bae, Eunjin, Takihara, Yoshihiro, Hirao, Atsushi, Oshima, Hiroko, Oshima, Masanobu, Ooshima, Akira, Sheen, Yhun Yhong, Kim, Seong‐Jin, Kim, Dae‐Kee
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768399/
https://www.ncbi.nlm.nih.gov/pubmed/26583567
http://dx.doi.org/10.1111/cas.12849
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author Naka, Kazuhito
Ishihara, Kaori
Jomen, Yoshie
Jin, Cheng Hua
Kim, Dong‐Hyun
Gu, Yoon‐Kang
Jeong, Eun‐Sook
Li, Shaoguang
Krause, Daniela S.
Kim, Dong‐Wook
Bae, Eunjin
Takihara, Yoshihiro
Hirao, Atsushi
Oshima, Hiroko
Oshima, Masanobu
Ooshima, Akira
Sheen, Yhun Yhong
Kim, Seong‐Jin
Kim, Dae‐Kee
author_facet Naka, Kazuhito
Ishihara, Kaori
Jomen, Yoshie
Jin, Cheng Hua
Kim, Dong‐Hyun
Gu, Yoon‐Kang
Jeong, Eun‐Sook
Li, Shaoguang
Krause, Daniela S.
Kim, Dong‐Wook
Bae, Eunjin
Takihara, Yoshihiro
Hirao, Atsushi
Oshima, Hiroko
Oshima, Masanobu
Ooshima, Akira
Sheen, Yhun Yhong
Kim, Seong‐Jin
Kim, Dae‐Kee
author_sort Naka, Kazuhito
collection PubMed
description Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benefits such CML‐LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW‐7197, an orally bioavailable transforming growth factor‐β signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML‐LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW‐7197 to CML‐affected mice significantly delayed disease relapse and prolonged survival. Notably, combined treatment with EW‐7197 plus TKI was effective in eliminating CML‐LICs even if they expressed the TKI‐resistant T315I mutant BCR‐ABL1 oncogene. Collectively, these results indicate that EW‐7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML‐LICs.
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spelling pubmed-47683992016-04-01 Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells Naka, Kazuhito Ishihara, Kaori Jomen, Yoshie Jin, Cheng Hua Kim, Dong‐Hyun Gu, Yoon‐Kang Jeong, Eun‐Sook Li, Shaoguang Krause, Daniela S. Kim, Dong‐Wook Bae, Eunjin Takihara, Yoshihiro Hirao, Atsushi Oshima, Hiroko Oshima, Masanobu Ooshima, Akira Sheen, Yhun Yhong Kim, Seong‐Jin Kim, Dae‐Kee Cancer Sci Original Articles Recent strategies for treating CML patients have focused on investigating new combinations of tyrosine kinase inhibitors (TKIs) as well as identifying novel translational research agents that can eradicate CML leukemia‐initiating cells (CML‐LICs). However, little is known about the therapeutic benefits such CML‐LIC targeting therapies might bring to CML patients. In this study, we investigated the therapeutic potential of EW‐7197, an orally bioavailable transforming growth factor‐β signaling inhibitor which has recently been approved as an Investigational New Drug (NIH, USA), to suppress CML‐LICs in vivo. Compared to TKI treatment alone, administration of TKI plus EW‐7197 to CML‐affected mice significantly delayed disease relapse and prolonged survival. Notably, combined treatment with EW‐7197 plus TKI was effective in eliminating CML‐LICs even if they expressed the TKI‐resistant T315I mutant BCR‐ABL1 oncogene. Collectively, these results indicate that EW‐7197 may be a promising candidate for a new therapeutic that can greatly benefit CML patients by working in combination with TKIs to eradicate CML‐LICs. John Wiley and Sons Inc. 2016-01-26 2016-02 /pmc/articles/PMC4768399/ /pubmed/26583567 http://dx.doi.org/10.1111/cas.12849 Text en © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Naka, Kazuhito
Ishihara, Kaori
Jomen, Yoshie
Jin, Cheng Hua
Kim, Dong‐Hyun
Gu, Yoon‐Kang
Jeong, Eun‐Sook
Li, Shaoguang
Krause, Daniela S.
Kim, Dong‐Wook
Bae, Eunjin
Takihara, Yoshihiro
Hirao, Atsushi
Oshima, Hiroko
Oshima, Masanobu
Ooshima, Akira
Sheen, Yhun Yhong
Kim, Seong‐Jin
Kim, Dae‐Kee
Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title_full Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title_fullStr Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title_full_unstemmed Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title_short Novel oral transforming growth factor‐β signaling inhibitor EW‐7197 eradicates CML‐initiating cells
title_sort novel oral transforming growth factor‐β signaling inhibitor ew‐7197 eradicates cml‐initiating cells
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4768399/
https://www.ncbi.nlm.nih.gov/pubmed/26583567
http://dx.doi.org/10.1111/cas.12849
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