{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:02:03Z","timestamp":1789984923178,"version":"4.0.1"},"reference-count":152,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U23A20499"],"award-info":[{"award-number":["U23A20499"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["U23A20499"],"award-info":[{"award-number":["U23A20499"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Zhejiang Provincial Leading Project for Leading Geese Plan","award":["2026C02A1089"],"award-info":[{"award-number":["2026C02A1089"]}]},{"name":"Transformation Project of the Chunyan Project","award":["CY202302"],"award-info":[{"award-number":["CY202302"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Gastric cancer metastasis and poor treatment responses are spatially heterogeneous; however, single-marker positivity, cellular enrichment, or simple colocalization alone is insufficient to establish a functionally meaningful spatial niche. Within this framework, \u201ctreatment resistance\u201d encompasses primary nonresponse, reduced treatment sensitivity, insufficient local drug delivery, post-treatment residual survival, acquired resistance, and interlesional differences in therapeutic efficacy. We propose a minimum criteria chain for candidate spatial niches comprising four elements: a specified spatial context; neighborhoods characterized using prespecified and transparently reported spatial rules; local functional programs concordant with these neighborhoods; and associations with malignant phenotypes or clinical outcomes. Based on the principle of linking dominant spatial contexts with their predominant malignant functional outputs, we summarize four candidate niches within primary tumors\u2014the invasive front\u2013tumor\u2013stroma interface, immune exclusion\u2013immune evasion, hypoxia\u2013metabolic adaptation, and perivascular supportive niches\u2014as well as an organ-context-dependent adaptive niche-forming process at metastatic sites. The level of evidence supporting these categories varies substantially. Immune-exclusion-related spatial states currently have relatively stronger links to treatment-response cohorts; however, rigorous gastric-cancer-specific in situ validation remains limited, and no candidate niche has yet achieved full clinical validation. Invasive-front and hypoxic niches are supported primarily by pathological or mechanistic evidence, whereas evidence for perivascular niches remains limited despite emerging longitudinal treatment-response observations, and metastatic niches outside the peritoneum require stronger longitudinal, local functional, and spatial-perturbation validation. This framework aims to standardize spatial-niche terminology and evidence interpretation and guide future quantification, validation, and potential clinical translation in gastric cancer.<\/jats:p>","DOI":"10.3390\/cells15181676","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T13:50:27Z","timestamp":1789566627000},"page":"1676","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Candidate Spatial Niches Associated with Gastric Cancer Metastasis and Treatment Resistance: Functional Classification, Evidence Boundaries, and a Translational Framework"],"prefix":"10.3390","volume":"15","author":[{"given":"Yi","family":"Huang","sequence":"first","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingcheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaheng","family":"Lou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo","family":"Bian","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingsi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taowei","family":"Gou","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Traditional Chinese Medicine \u201cPreventing Disease\u201d Wisdom Health Project Research Center of Zhejiang, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guangji","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Zhejiang Key Laboratory of Blood-Stasis-Toxin Syndrome, Zhejiang Chinese Medical University, Hangzhou 310053, China"},{"name":"Traditional Chinese Medicine \u201cPreventing Disease\u201d Wisdom Health Project Research Center of Zhejiang, Hangzhou 310053, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1186\/s12957-016-1042-y","article-title":"The patterns and timing of recurrence after curative resection for gastric cancer in China","volume":"14","author":"Liu","year":"2016","journal-title":"World J. 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