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Novel oral transforming growth factor- signaling inhibitor EW-7197 eradicates CML-initiating cells
- Title
- Novel oral transforming growth factor- signaling inhibitor EW-7197 eradicates CML-initiating cells
- Authors
- 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
- Ewha Authors
- 신윤용; 김대기
- SCOPUS Author ID
- 신윤용; 김대기
- Issue Date
- 2016
- Journal Title
- CANCER SCIENCE
- ISSN
- 1347-9032
1349-7006
- Citation
- CANCER SCIENCE vol. 107, no. 2, pp. 140 - 148
- Keywords
- ALK5 inhibitor; CML stem cells; relapse prevention; TGF- signaling; TKI resistance
- Publisher
- WILEY-BLACKWELL
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- 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- 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.
- DOI
- 10.1111/cas.12849
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
- Files in This Item:
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