Publication Name	World Journal of Gastroenterology
Manuscript ID	87228
Country	China

Category	Medicine, Research & Experimental
Manuscript Type	Basic Study
Article Title	Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis
Manuscript Source	Unsolicited Manuscript
All Author List	Zheng-Yan Yang, Yi-Wei Zhao, Jing-Rui Xue, Ran Guo, Zhi Zhao, Han-Di Liu, Zhi-Guang Ren and Ming Shi
Funding Agency and Grant Number	Funding Agency Grant Number Youth Fund of National Natural Science Foundation of China 81803575 Youth Fund of National Natural Science Foundation of China 31902287 Kaifeng Science and Technology Development Plan Project 2203008 College Students Innovation and Entrepreneurship Training Program of Henan University 20231022007 Key Specialized Research and Promotion Project of Henan Province in 2023 232102311205 Henan Medical Science and Technology Research Program Project LHGJ20210801
Corresponding Author	Zhi-Guang Ren, Doctor, Associate Professor, Department of Pathology, School of Basic Medical Science, Henan University, No. 1 Jinming Street, Kaifeng 475004, Henan Province, China. renzhiguang66@outlook.com
Key Words	Gastric cancer; Trastuzumab resistance; Thioridazine; S-phase kinase associated protein 2; Glycolysis
Core Tip	S-phase kinase-interacting protein 2 (Skp2) has been shown to be a reliable prognostic indicator of unfavorable outcomes for gastric cancer (GC). However, no agents specifically targeting Skp2 have been successfully developed. In this study, we proved that thioridazine restores the sensitivity of GC cells to trastuzumab both in vivo and in vitro by inhibiting Skp2-mediated glycolysis. Furthermore, the combination of thioridazine and lapatinib exhibits enhanced inhibitory effects compared with either monotherapy on the growth and survival of trastuzumab-resistant GC cells. Overall, this study suggests the potential of a thioridazine-based therapy to overcome trastuzumab resistance in human epidermal growth factor receptor 2-positive GC by targeting Skp2.
Citation	Yang ZY, Zhao YW, Xue JR, Guo R, Zhao Z, Liu HD, Ren ZG, Shi M. Thioridazine reverses trastuzumab resistance in gastric cancer by inhibiting S-phase kinase associated protein 2-mediated aerobic glycolysis. World J Gastroenterol 2023; 29(45): 5974-5987

Received	2023-09-17 15:07
Peer-Review Started	2023-09-17 15:08
To Make the First Decision
Return for Revision	2023-10-08 05:08
Revised	2023-10-19 12:17
Second Decision	2023-11-14 01:12
Accepted by Journal Editor-in-Chief
Accepted by Executive Editor-in-Chief	2023-11-17 08:50
Articles in Press	2023-11-17 08:50
Publication Fee Transferred
Edit the Manuscript by Language Editor
Typeset the Manuscript	2023-11-28 03:18

ISSN	1007-9327 (print) and 2219-2840 (online)
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