Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells
- 주제(키워드) ALK5 inhibitor , CML stem cells , Relapse prevention , TGF-β signaling , TKI resistance
- 등재 SCIE, SCOPUS
- 발행기관 Blackwell Publishing Ltd
- 발행년도 2016
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000123980
- 본문언어 영어
- Published As http://dx.doi.org/10.1111/cas.12849
- 저작권 이화여자대학교 논문은 저작권에 의해 보호받습니다.
초록/요약
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. © 2015 The Authors.
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