Publication Name	World Journal of Gastroenterology
Manuscript ID	118835
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Letter to the Editor
Article Title	Lysosomal vulnerability as a therapeutic axis for overcoming proteasome inhibitor resistance in gastric cancer
Manuscript Source	Invited Manuscript
All Author List	Wen-Wen Liu and Xiao-Jun Yang
Funding Agency and Grant Number	Funding Agency Grant Number Natural Science Foundation of Gansu Province No. 25JRRA304 Doctoral Fund of the Key Laboratory of Gastrointestinal Tumor Diagnosis and Treatment of the National Health Commission No. NHCDP2022001 the Doctoral Supervisor Cultivation Program of Gansu Provincial Hospital No. 22GSSYA-3
Corresponding Author	Xiao-Jun Yang, MD, PhD, Professor, Department of General Surgery, Gansu Provincial Hospital, No. 199 Donggang West Road, Chengguan District, Lanzhou 730000, Gansu Province, China. yangxjmd@aliyun.com
Key Words	Lysosomal vulnerability; Proteasome inhibitor resistance; Bortezomib; Gastric cancer; Transcription factor EB; Patient-derived organoids
Core Tip	Proteasome inhibitor resistance in solid tumors remains a major therapeutic challenge. This letter highlights lysosomal vulnerability as a central adaptive mechanism underlying bortezomib resistance in gastric cancer. By reframing lysosomes as active regulators of proteotoxic stress and drug sequestration rather than passive degradative organelles, the discussed study supports lysosome-targeted strategies as a promising therapeutic axis. Patient-derived organoid validation further underscores the translational relevance of intercepting lysosome-centered stress adaptation to enhance proteasome inhibitor efficacy.
Citation	Liu WW, Yang XJ. Lysosomal vulnerability as a therapeutic axis for overcoming proteasome inhibitor resistance in gastric cancer. World J Gastroenterol 2026; In press

Received	2026-01-13 03:34
Peer-Review Started	2026-01-13 03:34
First Decision by Editorial Office Director	2026-01-21 09:33
Return for Revision	2026-01-21 09:33
Revised	2026-01-27 06:43
Publication Fee Transferred
Second Decision by Editor	2026-02-28 02:32
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-02-28 04:42
Articles in Press	2026-02-28 04:42
Edit the Manuscript by Language Editor
Typeset the Manuscript

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