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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, KazuhitoIshihara, KaoriJomen, YoshieJin, Cheng HuaKim, Dong-HyunGu, Yoon-KangJeong, Eun-SookLi, ShaoguangKrause, Daniela S.Kim, Dong-WookBae, EunjinTakihara, YoshihiroHirao, AtsushiOshima, HirokoOshima, MasanobuOoshima, AkiraSheen, Yhun YhongKim, Seong-JinKim, Dae-Kee
Ewha Authors
신윤용김대기
SCOPUS Author ID
신윤용scopus; 김대기scopus
Issue Date
2016
Journal Title
CANCER SCIENCE
ISSN
1347-9032JCR Link1349-7006JCR Link
Citation
vol. 107, no. 2, pp. 140 - 148
Keywords
ALK5 inhibitorCML stem cellsrelapse preventionTGF- signalingTKI resistance
Publisher
WILEY-BLACKWELL
Indexed
SCI; SCIE; SCOPUS WOS scopus
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
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