Choosing the right animal model for sarcoma research.

Abstract

Sarcomas comprise over 100 mesenchymal malignancies characterised by extreme genomic heterogeneity, ranging from fusion-driven paediatric tumours to highly unstable adult leiomyosarcomas. This genetic complexity shapes tumour behaviour, influences growth and metastasis, and determines how patients respond to therapy. Accurate animal models must reflect not only the molecular characteristics of these tumours, but also their microenvironment and dynamic interaction with the host immune system. The diversity of this group of cancers presents different challenges for animal model selection, particularly as sarcoma-specific resources are very limited. Therefore, we have reviewed in detail several types of models, including: syngeneic (e.g., MCA205 and KRIMS series), chemically induced (e.g., MCA, DMBA), cell-derived xenografts (CDX; e.g., KCS8 and KCS9 osteosarcoma lines), patient-derived xenograft (PDX; e.g., pleomorphic leiomyosarcoma and GIST models), including humanised PDX (huPDX; e.g. HuNOG-EXL), and zebrafish (e.g. tp53M214K PNST and EWS-FLI1 transgenics) - to illustrate their sarcoma-specific use cases and discuss their advantages and limitations. Genetically engineered models and their development are not a subject of this review, as they represent a very broad subject independently and are discussed elsewhere.