Publication Name	World Journal of Gastroenterology
Manuscript ID	120028
Country	China

Category	Gastroenterology & Hepatology
Manuscript Type	Opinion Review
Article Title	Tumor-node response heterogeneity: Exploring the “spatial biology” of neoadjuvant therapy response in rectal cancer and its clinical implications
Manuscript Source	Invited Manuscript
All Author List	Rui-Gang Wang
Funding Agency and Grant Number	Funding Agency Grant Number Beijing Tsinghua Changgung Hospital Youth Fund 12021C1011 Research Funding Program for Young and Mid-Career Physicians in AI-Assisted Healthcare 12060C0004 Capital Medical Science and Technology Innovation Achievement Transformation Promotion Program YC202501QX0920
Corresponding Author	Rui-Gang Wang, MD, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, No. 168 Litang Road, Changping District, Beijing 102218, China. doctorwrg@163.com
Key Words	Rectal cancer; Lymph node regression grade; Spatial biology; Tumor microenvironment; Precision oncology
Core Tip	This review article presents a spatial biology framework that explains why primary tumors and metastatic lymph nodes in locally advanced rectal cancer often respond differently to neoadjuvant chemoradiotherapy. Key points include clarifying the mechanisms of immune evasion and mitochondrial genome dynamics, and integrating tumor and lymph node regression grades to define spatial response phenotypes. The framework enhances prognostic stratification, as evident in the nodal sanctuary phenotype, and facilitates tailored therapeutic strategies through a translational roadmap that includes circulating tumor genetic material-guided therapy and lymph node-sparing radiotherapy trials. Ultimately, this approach aims to advance compartment-aware, biology-driven precision oncology in rectal cancer.
Citation	Wang RG. Tumor-node response heterogeneity: Exploring the “spatial biology” of neoadjuvant therapy response in rectal cancer and its clinical implications. World J Gastroenterol 2026; In press

Received	2026-02-24 01:21
Peer-Review Started	2026-02-24 01:22
First Decision by Editorial Office Director	2026-03-09 09:15
Return for Revision	2026-03-09 09:15
Revised	2026-04-01 15:11
Publication Fee Transferred
Second Decision by Editor	2026-05-07 03:24
Second Decision by Editor-in-Chief
Final Decision by Editorial Office Director	2026-05-07 09:16
Articles in Press	2026-05-07 09:16
Edit the Manuscript by Language Editor
Typeset the Manuscript

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