Publication Name	World Journal of Gastrointestinal Oncology
Manuscript ID	121282
DOI	10.4251/wjgo.121282
Country	China

Category	Medicine, Research & Experimental
Manuscript Type	Basic Study
Article Title	Targeting cyclin-dependent kinase 6 partially reverses drug resistance in ripretinib-resistant gastrointestinal stromal tumor cells in vitro
Manuscript Source	Unsolicited Manuscript
All Author List	Xiao-Dong Wang, Chun-Hui Shou, Sheng-Chuan Chen, Yan-Yun Hong, Kan-Kai Zhu, Wei-Li Yang and Ji-Ren Yu
Funding Agency and Grant Number	Funding Agency Grant Number National Natural Science Foundation of China 82001695 Beijing Xisike Clinical Oncology Research Foundation Y-zai2021/ms-0133
Corresponding Author	Ji-Ren Yu, Associate Chief Physician, Associate Research Scientist, Director, MD, PhD, Researcher, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, No. 79 Qingchun Road, Hangzhou 310000, Zhejiang Province, China. yujr0909@zju.edu.cn
Key Words	Combination therapy; Apoptosis; Drug resistance; Protein kinase B signaling pathway; Cyclin-dependent kinase 6; Ripretinib; Gastrointestinal stromal tumor
Core Tip	This study identifies cyclin-dependent kinase 6 (CDK6) as a key mediator of ripretinib resistance in gastrointestinal stromal tumors (GIST), with its overexpression driven by protein kinase B hyperactivation. CDK6 inhibitor induces G1-phase cell cycle arrest and apoptosis in ripretinib-resistant GIST cells, and combining CDK6 inhibitor palbociclib with ripretinib exerts a synergistic effect to reverse resistance, restoring the tumor cells’ sensitivity to ripretinib. This uncovers the protein kinase B/CDK6 axis as a novel target for treating ripretinib-resistant GIST, providing a new precision therapy strategy.
Citation	Wang XD, Shou CH, Chen SC, Hong YY, Zhu KK, Yang WL, Yu JR. Targeting cyclin-dependent kinase 6 partially reverses drug resistance in ripretinib-resistant gastrointestinal stromal tumor cells in vitro. World J Gastrointest Oncol 2026; In press DOI: https://doi.org/10.4251/wjgo.121282

Received	2026-03-23 06:48
Peer-Review Started	2026-03-23 06:48
First Decision by Editorial Office Director	2026-04-16 07:48
Return for Revision	2026-04-17 01:34
Revised	2026-05-11 00:40
Publication Fee Transferred	2026-05-21 01:43
Second Decision by Editor	2026-06-12 02:34
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-06-12 06:13
Articles in Press	2026-06-12 06:13
Edit the Manuscript by Language Editor
Typeset the Manuscript

ISSN	1948-5204 (online)
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