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World J Gastroenterol. Sep 7, 2026; 32(33): 118835
Published online Sep 7, 2026. doi: 10.3748/wjg.118835
Published online Sep 7, 2026. doi: 10.3748/wjg.118835
Letter to the Editor: Lysosomal vulnerability as a therapeutic axis for overcoming proteasome inhibitor resistance in gastric cancer
Wen-Wen Liu, The First Clinical Medical School, Gansu University of Chinese Medicine, Lanzhou 730000, Gansu Province, China
Wen-Wen Liu, Xiao-Jun Yang, Department of General Surgery, Gansu Provincial Hospital, Lanzhou 730000, Gansu Province, China
Author contributions: Liu WW designed the overall concept and outline of the manuscript; Yang XJ contributed to the discussion and design of the manuscript; Liu WW and Yang XJ contributed to this paper, the writing, and editing the manuscript and review of literature.
Supported by 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; and the Doctoral Supervisor Cultivation Program of Gansu Provincial Hospital, No. 22GSSYA-3.
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
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
Received: January 13, 2026
Revised: January 27, 2026
Accepted: February 28, 2026
Published online: September 7, 2026
Processing time: 209 Days and 9.2 Hours
Revised: January 27, 2026
Accepted: February 28, 2026
Published online: September 7, 2026
Processing time: 209 Days and 9.2 Hours
Core Tip
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.