Mapping molecular landscapes in triple-negative breast cancer: insights from spatial transcriptomics.

The tumor microenvironment (TME) of triple-negative breast cancer (TNBC) is a highly heterogeneous and very aggressive form of the disease that has few suitable treatment options; however, spatial transcriptomics (ST) is a powerful tool for elucidation of the TME in TNBC. Because of its spatial context preservation, ST has a unique capability to map tumor-stroma interactions, immune infiltration, and therapy resistance mechanisms (which are key to understanding TNBC progression), compared with conventional transcriptomics. This review shows the use of ST in TNBC, its utilization in spatial biomarker identification, intratumoral heterogeneity definition, molecular subtyping refinement, and prediction of immunotherapy responses. Recent insight from ST-driven insights has explained the key spatial patterns on immune evasion, chemotherapy resistance, racial disparities of TNBC, and aspects for patient stratification and therapeutic decision. With the integration of ST with the subjects of proteomics and imaging mass cytometry, this approach has been enlarged and is now applied in precision medicine and biomarker discovery. Recently, advancements in AI-based spatial analysis for tumor classification, identification of biomarkers, and creation of therapy prediction models have occurred. However, continued developments in ST technologies, computational tools, and partnerships amongst multiple centers to facilitate the integration of ST into clinical routine practice are needed to unlock novel therapeutic targets.