Novel oral transforming growth factor-β signaling inhibitor EW-7197 eradicates CML-initiating cells

Kazuhito Naka, Kaori Ishihara, Yoshie Jomen, Cheng Hua Jin, Dong Hyun Kim, Yoon Kang Gu, Eun Sook Jeong, Shaoguang Li, Daniela S. Krause, Dong Wook Kim, Eunjin Bae, Yoshihiro Takihara, Atsushi Hirao, Hiroko Oshima, Masanobu Oshima, Akira Ooshima, Yhun Yhong Sheen, Seong Jin Kim, Dae Kee Kim

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25 Scopus citations


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.

Original languageEnglish
Pages (from-to)140-148
Number of pages9
JournalCancer Science
Issue number2
StatePublished - 1 Feb 2016

Bibliographical note

Publisher Copyright:
© 2016 Japanese Cancer Association.


  • ALK5 inhibitor
  • CML stem cells
  • Relapse prevention
  • TGF-β signaling
  • TKI resistance


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