Division of Hematology Oncology, Department of Medicine
Cancer Biology | Hematology | Hemic and Lymphatic Diseases | Neoplasms | Oncology
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-beta 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.
ALK5 inhibitor, CML stem cells, TGF-β signaling, TKI resistance, relapse prevention
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© 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 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.
DOI of Published Version
Cancer Sci. 2016 Feb;107(2):140-8. doi: 10.1111/cas.12849. Epub 2016 Jan 26. Link to article on publisher's site
Naka, Kazuhito; Li, Shaoguang; and Kim, Dae-Kee, "Novel oral transforming growth factor-beta signaling inhibitor EW-7197 eradicates CML-initiating cells" (2016). Open Access Articles. 2755.
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This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.