Soft tissue sarcomas at the single-cell and spatial resolution: new markers and targets

Soft tissue sarcomas (STS) are heterogeneous and aggressive tumors, originating in connective tissues embryologically derived from the mesenchyme. Due to their rarity, crucial information about their biology is still lacking. In recent years, single-cell and spatial analyses have opened up new horizons in oncology, leading to the possibility of characterizing the internal architecture of the tumor at the single-cell and spatial levels. This review summarizes the first results acquired through these revolutionary methods for different types of STS. We discuss tumor cell populations and their evolution, interactions between tumor cells and the microenvironment, new prognostic markers, and clinically important targets. Finally, we examine the challenges presented by the single-cell and spatial omics of STS and the future perspectives in this field. © 2025 Elsevier B.V., All rights reserved.