Novel oral transforming growth factor‐β signaling inhibitor EW ‐7197 eradicates CML ‐initiating cells
Year: 2015
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-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.
Source: Cancer Science
DOI: 10.1111/cas.12849
Authors: 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
Institutions: Kanazawa University, Hiroshima University, Cancer Research Institute of Kanazawa University, Research Institute for Radiation Biology and Medicine, Hiroshima University, Ewha Womans University, Inje University, The Catholic University of Korea Seoul St. Mary's Hospital, Catholic University of Korea, University of Massachusetts Chan Medical School, Goethe University Frankfurt, Georg Speyer Haus, CHA University
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,600
Awards: G2684204861, SOX17 suppression and inflammation in malignant cancer progression, G5642099630, Stem cell-specific phosphorylation of Smad3 for regulating self-renewal capacity in CML stem cells, Establishment of novel gastric cancer mouse models, A study of microenvironment for maintenance or acquisition of malignant property
OpenAlex ID: W2172546656