TY  - EJOU
AU  - Zhang, Zhewei 
AU  - Wu, Jie 
AU  - Chan, Kit Ying 
AU  - Lau, Tat San 
AU  - Wang, Chi Chiu 

TI  - Spatial Multi-Omics Dissecting Drug Resistance and Therapeutic Vulnerability in Ovarian Cancer: Insights Primarily from High-Grade Serous Carcinoma
T2  - Oncology Research

PY  - 
VL  - 
IS  - 
SN  - 1555-3906

AB  - Drug resistance in ovarian cancer, particularly platinum and immunotherapy resistance, is not a uniform tumor property but arises from spatially discrete microenvironmental niches. Conventional bulk and single-cell sequencing approaches cannot resolve this spatial organization, obscuring the regional heterogeneity that governs therapeutic vulnerability. Spatial multi-omics technologies, including spatial transcriptomics, multiplexed spatial proteomics, and mass spectrometry imaging-based metabolomics, now enable direct interrogation of these resistance niches within intact tissue architecture. This review aims to synthesize how spatial multi-omics redefines the mechanistic understanding of platinum and immunotherapy resistance in ovarian cancer and to propose a framework of spatially resolved biomarkers for niche-specific patient stratification. In high-grade serous ovarian carcinoma, four principal resistance microdomains have been proposed: the perivascular cancer stem-like cell niche, the hypoxic HIF-1α/NRF2/glutathione-rich niche, the cancer-associated fibroblast barrier niche mediating immune exclusion, and the omental adipocyte niche driving fatty acid oxidation-dependent chemoresistance. Spatial analysis further reveals that tertiary lymphoid structures (TLSs) in ovarian cancer harbor terminally exhausted rather than progenitor T cells, which may help to explain paradoxical immunotherapy failure despite immune infiltration. Integration of spatial transcriptomic, proteomic, and metabolomic data generates candidate biomarker scores, including spatial immune infiltration, cancer-associated fibroblast (CAF) organization, metabolic niche, chemoresistance niche, and spatial heterogeneity scores, that are presented here as hypothesis-generating research tools for niche-specific stratification rather than as clinical decision rules. Prospective validation of these spatial biomarkers in clinical trial cohorts represents the critical next step toward spatially informed precision oncology in ovarian cancer.
KW  - Spatial multi-omics; drug resistance; tumor microenvironment (TME); ovarian cancer; immunotherapy resistance

DO  - 10.32604/or.2026.085305