Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
World J Gastrointest Oncol. Sep 15, 2026; 18(9): 121282
Published online Sep 15, 2026. doi: 10.4251/wjgo.121282
Published online Sep 15, 2026. doi: 10.4251/wjgo.121282
Targeting cyclin-dependent kinase 6 partially reverses drug resistance in ripretinib-resistant gastrointestinal stromal tumor cells in vitro
Xiao-Dong Wang, Chun-Hui Shou, Sheng-Chuan Chen, Yan-Yun Hong, Kan-Kai Zhu, Wei-Li Yang, Ji-Ren Yu, Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310000, Zhejiang Province, China
Co-first authors: Xiao-Dong Wang and Chun-Hui Shou.
Author contributions: Wang XD and Shou CH contributed to data processing and article writing, and they contributed equally to this manuscript and are co-first authors; Chen SC, Hong YY, Zhu KK, and Yang WL collected and organized data; Yu JR provided ideas and revised the manuscript. All authors have read and approved the final version to be published.
AI contribution statement: Grammarly and Wordvice were used for language polishing. No AI tool was involved in the generation of research data, interpretation of results, or formulation of conclusions.
Supported by National Natural Science Foundation of China, No. 82001695; and Beijing Xisike Clinical Oncology Research Foundation, No. Y-zai2021/ms-0133.
Institutional review board statement: This cell experiment using cell lines donated by Wen-Bin Ou complies with ethical regulations. No banned operations like human reproductive cloning are involved, meeting exemption criteria. The study is approved for ethical review exemption by the Ethics Committee of the First Affiliated Hospital, Zhejiang University School of Medicine, with official certification attached. We strictly follow ethical rules and accept supervision.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: The data that support the findings of our study are available from the corresponding author.
Corresponding author: Ji-Ren Yu, MD, PhD, Associate Chief Physician, Associate Research Scientist, Director, 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
Received: March 23, 2026
Revised: May 11, 2026
Accepted: June 12, 2026
Published online: September 15, 2026
Processing time: 158 Days and 14.8 Hours
Revised: May 11, 2026
Accepted: June 12, 2026
Published online: September 15, 2026
Processing time: 158 Days and 14.8 Hours
Core Tip
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.