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Zhang YY, Yu YG, Dang YQ, Hu D. Letter to the editor: Causal and translational considerations for Xiangshaliujunzi decoction-mediated PANoptosis in 5-fluorouracil-resistant gastric cancer. World J Gastrointest Oncol 2026; 18(12): 125392 [DOI: 10.4251/wjgo.125392]
World J Gastrointest Oncol. Dec 15, 2026; 18(12): 125392 Published online Dec 15, 2026. doi: 10.4251/wjgo.125392
Letter to the editor: Causal and translational considerations for Xiangshaliujunzi decoction-mediated PANoptosis in 5-fluorouracil-resistant gastric cancer
Yu-Yi Zhang, Yi-Ge Yu, Yan-Qi Dang, Dan Hu
Yu-Yi Zhang, Yi-Ge Yu, Yan-Qi Dang, Dan Hu, 7 LAB Joint Laboratory, Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, China
Yan-Qi Dang, State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
Co-corresponding authors: Yan-Qi Dang and Dan Hu.
Author contributions: Zhang YY contributed to the letter writing; Yu YG and Hu D contributed to the reviewing; Dang YQ contributed to the letter revision. Dang YQ and Hu D contributed equally to this work as co-corresponding authors.
AI contribution statement: AI tools were used solely to assist with language polishing and grammatical refinement. All authors were responsible for and agree to be accountable for all scientific content.
Supported by the Science and Technology Development Fund of Shanghai Pudong New Area, No. PKJ2024-Y19; the Investigator-Initiated Trial Program of Shanghai Pudong New Area Health Commission, the Cohort Study Program, No. 2025-PWDL-03; the National Pilot Zone for Inheritance, Innovation and Development of Traditional Chinese Medicine in Pudong New Area, No. PDZY-2026-0318; and the Science and Technology Development Project of Shanghai University of Traditional Chinese Medicine, No. 25KFL82.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Yan-Qi Dang, PhD, 7 LAB Joint Laboratory, Seventh People’s Hospital, Shanghai University of Traditional Chinese Medicine, No. 358 Datong Road, Pudong New Area, Shanghai 200137, China. yq_dang@shutcm.edu.cn
Received: July 7, 2026 Revised: August 27, 2026 Accepted: October 12, 2026 Published online: December 15, 2026 Processing time: 126 Days and 9.9 Hours
Abstract
The recent study by Gao et al reported that Xiangshaliujunzi decoction (XSLJZD) may overcome 5-fluorouracil (5-FU) resistance in gastric cancer in association with the miR-200a-3p/ZEB1/IRF1 axis and PANoptosis-associated signaling. This letter focuses on three related but distinct evidentiary questions: The causal role of IRF1 in PANoptotic signaling, the pharmacological interpretation of the XSLJZD/5-FU combination, and the clinical relevance of the proposed molecular axis. We discuss these issues as different levels of inference and propose experimentally testable strategies to distinguish mechanistic association from therapeutic causality.
Core Tip: Gao et al reported that Xiangshaliujunzi decoction may overcome 5-fluorouracil resistance in gastric cancer through the miR-200a-3p/ZEB1/IRF1 axis and PANoptosis-associated signaling. This letter focuses on three evidentiary levels: Mechanistic causality, pharmacological interaction, and clinical relevance. We propose pathway-specific genetic validation, standardized drug exposure with quantitative combination analysis, preparation-level characterization, and independent clinical validation. These approaches may help determine whether the proposed molecular axis represents a therapeutically actionable mechanism rather than an associated molecular signature.
