[Spatial Transcriptome Analysis in Cancer and Technology Development]

Spatial transcriptomics technologies enable omics analysis while preserving the spatial and histopathological context of cells within tissue sections, and have rapidly become widespread across various research fields, including cancer research. In cancer studies, these technologies are widely employed to elucidate changes in cancer cells and the surrounding tumor microenvironment associated with tumor progression and the emergence of therapeutic resistance. Through the application of spatial transcriptomics, numerous novel insights have been obtained regarding the identification of therapeutic targets and strategies to overcome treatment resistance. Sequencing-based platforms such as Visium capture transcriptome-wide information with spatial coordinates and have been applied to characterize the microenvironmental dynamics during lung adenocarcinoma progression and to identify microenvironmental states contributing to chemotherapy resistance in ovarian clear cell carcinoma. Imaging-based platforms such as Xenium and CosMx enable single-cell-resolution profiling of gene expression across hundreds of thousands of cells within tissue sections without requiring cell dissociation, and can be combined with multiplexed immunofluorescence staining to simultaneously obtain gene expression and protein expression data from the same section. These approaches have facilitated the discovery of novel cell subsets associated with patient prognosis and the detection of micrometastatic cancer cells in lymph nodes. In addition to the expanding range of applications, the technologies themselves have undergone remarkable development. Emerging techniques include spatial full-length transcriptome sequencing for splice isoform and immune receptor repertoire analysis, RNA-based mutation detection, spatial epigenomic profiling of chromatin accessibility and DNA methylation, and 3-dimensional spatial transcriptomics for volumetric tissue analysis. This review provides an overview of the fundamental technologies underlying spatial transcriptomics, presents representative examples of their application in cancer research, and introduces next-generation measurement techniques that are expected to further advance the field.