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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...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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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. |
format | Online Article Text |
id | pubmed-4768399 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
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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