Integrative spatial multi-omics reveals the tumor ecosystem: From mechanistic insights to therapeutic strategies

Tumor heterogeneity and complex microenvironment interactions drive malignant progression and therapeutic resistance. Traditional omics technologies struggle to capture this complexity due to the loss of spatial molecular context. Spatial multi-omics technologies enable the simultaneous <i>in situ</i> analysis of gene expression, metabolic activity, and protein function within tissue, thereby transforming cancer research. This review systematically discusses the principles and applications of spatial transcriptomics, spatial metabolomics, spatial proteomics, and their integration. These approaches have revealed spatially driving mechanisms, such as the niche at the invasive front, dynamic evolution of the immune microenvironment, and cell-cell communication networks in metastatic spread. We also highlight their potential to promote precise tumor treatment including guiding patient stratification, optimizing treatment regimens, and overcoming drug resistance. Finally, we discuss the current challenges and future development directions. This study aims to clarify how spatial multi-omics deepens the understanding of tumor biology and accelerates clinical translation through multi-dimensional information integration.