Introduction to animal modelling: factors and tools for choosing the optimal model for sarcoma research-a...

Most sarcomas have complex karyotypes, making them particularly challenging to study and treat due to their genetic diversity and aggressive nature. Animal models are essential in sarcoma research as they provide a comprehensive approach to studying tumour biology, progression and therapeutic responses that cannot be fully replicated in vitro. However, choosing the right model requires consideration of many practical aspects that have not been adequately addressed, particularly in sarcomas. Therefore, we aim to fill this gap by focusing on several animal models used in sarcoma research.

We performed a literature search in Scopus, MEDLINE and Web of Science using specific search terms to identify published original in vivo studies regarding different sarcoma subtypes, as well as selection tools.

The most commonly used models are: syngeneic, genetically engineered mouse (GEM), chemically induced, cell-derived xenografts (CDX), patient-derived xenografts (PDX), humanised PDX (huPDX), and zebrafish. Each model has its own advantages, for example: CDXs enable high-throughput drug screening, PDXs preserve tumour heterogeneity in patients, while huPDXs most closely resemble the human immune response, However, there are various limitations to each model, including a lack of genetic diversity in syngeneic models, the complexity and time requirements of GEMs, and the short life span of cost-effective zebrafish. We also described various tools that can be used to help select the right animal model, including the International Mouse Strain Resource (ISMR) and the Mouse Tumour Biology Database (MTB), and inoculation methods (e.g., subcutaneus, orthopic).

With the right model, researchers can accurately study tumour behaviour, therapeutic responses and the basic mechanisms that underlie sarcoma development. We provide a practical guide for animal model selection though detailed discussion of model classes, inoculation routes, and endpoint to sarcoma-specific use cases as well as a list of active repositories/databases.