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; 32(41): 120028 [DOI: 10.3748/wjg.120028]
Corresponding Author of This Article
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
Research Domain of This Article
Gastroenterology & Hepatology
Article-Type of This Article
review-article
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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; 32(41): 120028 [DOI: 10.3748/wjg.120028]
World J Gastroenterol. Nov 7, 2026; 32(41): 120028 Published online Nov 7, 2026. doi: 10.3748/wjg.120028
Tumor-node response heterogeneity: Exploring the “spatial biology” of neoadjuvant therapy response in rectal cancer and its clinical implications
Rui-Gang Wang
Rui-Gang Wang, Department of Gastroenterology, Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua Medicine, Tsinghua University, Beijing 102218, China
Author contributions: Wang RG contributed to writing, revising, and reviewing this manuscript.
Supported by Beijing Tsinghua Changgung Hospital Youth Fund, No. 12021C1011; Research Funding Program for Young and Mid-Career Physicians in AI-Assisted Healthcare, No. 12060C0004; and Capital Medical Science and Technology Innovation Achievement Transformation Promotion Program, No. YC202501QX0920.
Conflict-of-interest statement: The author reports no relevant conflicts of interest for this article.
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
Received: February 24, 2026 Revised: April 1, 2026 Accepted: May 7, 2026 Published online: November 7, 2026 Processing time: 209 Days and 6.5 Hours
Core Tip
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.
