Evidence map›Paper›PMID 42279331›Full record

ReviewCancers2026

Architectural Refuges: Mapping Spatial Heterogeneity and Niche-Mediated Drug Resistance in Gastric and Esophageal Adenocarcinomas.

Krishnapriya Thangaretnam, Md Obaidul Islam, Jialun Lv, Lei Chen, Farah Ballout, Shoumin Zhu, Heng Lu, Dunfa Peng, Wael El-Rifai, Zheng Chen

Abstract readReview
In one paragraph

Review in Cancers, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors.

Krishnapriya ThangaretnamDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0001-9078-3915
Md Obaidul IslamDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0001-6560-5930
Jialun LvDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0009-0004-4848-9404
Lei ChenDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0009-0008-8096-7401
Farah BalloutDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0002-6399-9179
Shoumin ZhuDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.
Heng LuDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0009-0000-6562-4277
Dunfa PengDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0002-2182-7221
Wael El-RifaiDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0003-2101-6098
Zheng ChenDepartment of Surgery, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL 33136, USA.ORCID 0000-0002-6582-847X

Funding

DeGregorio Family Foundation Zheng_Chen_2025Florida Department of Health 24K05Gastric Cancer Foundation Zheng_2025The Mark Foundation for Cancer Research ASP24-0000000013
6 · The paper itself

Abstract

Resistance to systemic therapy remains the defining challenge in the management of gastric cancer (GC) and esophageal adenocarcinoma (EAC). While genomic drivers of resistance are well characterized, traditional bulk profiling has failed to capture the physical rules governing tumor survival within the complex tissue ecosystem. Emerging data from 2024-2025, leveraging high-resolution spatial transcriptomics and multi-omics, have recontextualized resistance as a phenomenon of "spatial privilege" rather than solely an intrinsic cellular fate. This review summarizes recent evidence to define "architectural refuges": distinct spatial niches that physically shield malignant clones from cytotoxic and targeted agents. We delineate three critical resistance domains common to upper gastrointestinal adenocarcinomas: (1) The "Excluded" Niche, where specific cancer-associated fibroblast (CAF) subpopulations (iCAFs vs. myCAFs) and stiffened extracellular matrix create hypovascular zones that limit drug delivery; (2) the "Immune-Tolerant" Niche, characterized by the spatial exclusion of CD8+ T cells and the recruitment of suppressive myeloid populations via the MIF/CD74 and USP14 axes; and (3) the "Metabolic" Niche, where mitochondrial heterogeneity and lipid metabolic symbiosis establish nutrient-deprived niches that select for stem-like, dormant states. By mapping these conserved spatial determinants from primary GEJ tumors to peritoneal and distant metastases, we argue that overcoming resistance requires an advancement: moving beyond targeting individual mutations to dismantling the multicellular architecture that sustains malignancy.

Indexed as

cancer-associated fibroblastsdrug resistancegastroesophageal adenocarcinomametabolic reprogrammingspatial nichespatial transcriptomicstumor microenvironment

Identifiers

PMID42279331
PMCPMC13255619

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.