Inhibition of glycolysis by a novel EGFR/HER2 inhibitor KU004 suppresses the growth of HER2+ cancer.

Upregulation of glycolysis was often observed in human HER2-overexpressing cancers. In this study, we demonstrated that KU004, a dual novel EGFR/HER2 inhibitor, disrupted cancer cell proliferation via modulation of glycolysis. KU004, inhibited the Warburg effect by suppressing hexokinase II (HK2) expression at the transcriptional and post-translational levels. Further study demonstrated that the downregulation of HKII by KU004 was mainly mediated by the PI3K/Akt signaling pathway. Furthermore, the role of HKII downregulation in KU004-mediated antitumor effect was also confirmed in our in vivo xenograft model. Collectively, these data suggest that multifaceted targeting the aberrant glucose metabolism along with the upstream HER2 may be an effective approach for clinical treatment against HER2+ cancer. Copyright © 2017 Elsevier Inc. All rights reserved.

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Chongchong Tian, Ziqiao Yuan, Dengqiu Xu, Pingping Ding, Tao Wang, Luyong Zhang, Zhenzhou Jiang. Inhibition of glycolysis by a novel EGFR/HER2 inhibitor KU004 suppresses the growth of HER2+ cancer. Experimental cell research. 2017 Aug 15;357(2):211-221

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PMID: 28532652

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