Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells
© 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2016 |
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| Erschienen: |
2016 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:107 |
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| Enthalten in: |
Cancer science - 107(2016), 2 vom: 04. Feb., Seite 140-8 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Naka, Kazuhito [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.07.2016 Date Revised 03.12.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1111/cas.12849 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM254771815 |
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| 245 | 1 | 0 | |a Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2015 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. | ||
| 520 | |a 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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| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
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| 700 | 1 | |a Jomen, Yoshie |e verfasserin |4 aut | |
| 700 | 1 | |a Jin, Cheng Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dong-Hyun |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Yoon-Kang |e verfasserin |4 aut | |
| 700 | 1 | |a Jeong, Eun-Sook |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Shaoguang |e verfasserin |4 aut | |
| 700 | 1 | |a Krause, Daniela S |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dong-Wook |e verfasserin |4 aut | |
| 700 | 1 | |a Bae, Eunjin |e verfasserin |4 aut | |
| 700 | 1 | |a Takihara, Yoshihiro |e verfasserin |4 aut | |
| 700 | 1 | |a Hirao, Atsushi |e verfasserin |4 aut | |
| 700 | 1 | |a Oshima, Hiroko |e verfasserin |4 aut | |
| 700 | 1 | |a Oshima, Masanobu |e verfasserin |4 aut | |
| 700 | 1 | |a Ooshima, Akira |e verfasserin |4 aut | |
| 700 | 1 | |a Sheen, Yhun Yhong |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Seong-Jin |e verfasserin |4 aut | |
| 700 | 1 | |a Kim, Dae-Kee |e verfasserin |4 aut | |
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