Experimental models of tumor growth in soft tissue sarcomas

Abstract

Soft tissue sarcomas are rare tumors (about 1 % of all malignant neoplasms) and include more than 70 histological subtypes, the pathogenetic features of which remain unclear. This is largely due to both quantity and volume of clinical material and high heterogeneity of the disease. Given the rarity and heterogeneity of each individual subtype of soft tissue sarcoma, there is an urgent need to develop universal model systems to understand the molecular changes that determine tumor biology. Such systems include CDX models (cell line-derived xenograft), created from cell lines, PDX (patient-derived xenograft), obtained from primary tumor/metastasis cells, both a whole fragment of surgical material and from a cell suspension; humanized animals containing various human immune cells, and GEM (genetically engineered mouse) models, which are created through transfection of genetic changes characteristic of different subtypes of soft tissue sarcomas. To create these systems, not only widely available mouse models are used, but also other animals, such as fish (Danio rerio) , rats, pigs, and dogs. Another important goal of using animal models is to screen the effectiveness of modern drugs. To date, treatment of various subtypes of soft tissue sarcomas is based on standard protocols of chemotherapy (doxorubicin, epirubicin, dacarbazine, ifosfamide) and surgical resection. In the case of inoperable forms or late stages of soft tissue sarcomas, animal models are a potential tool in predicting the effectiveness of therapy and personalized selection of treatment regimens. In this regard, studies of the mechanisms of targeted action on specific molecules and the use of humanized animals for the development of new approaches to immunotherapy are of particular relevance. The current review discusses animal model systems of the three most common types of soft tissue sarcomas: liposarcomas, undifferentiated pleomorphic and synovial sarcomas, as well as the use of these models to find new therapeutic solutions. Conclusion. Currently, PDX and GEM models are widely used to identify molecules and signaling pathways involved in the development of sarcomas, identify tumor-initiating cells, and assess the chemoresistance of known drugs and new drugs at the level of the entire tumor ecosystem. However, the key problems of animal models of soft tissue sarcomas remain changes in their composition and phenotype compared to the original tumor, poor survival of surgical material, and lack of cellular immunity in immunocompetent models, high cost, and the length of time it takes to create and maintain the model. A solution to one of the problems may be the use of humanized animals with PDX, which implies the presence in the model of immune, stromal and tumor components that are as close as possible to the human body.

Keywords

• soft tissue sarcomas
• in vivo models
• therapy