Preclinical models for the study of pediatric solid tumors: focus on bone sarcomas

Abstract

Sarcomas comprise between 10-15% of all pediatric malignancies. Osteosarcoma and Ewing sarcoma are the two most common pediatric bone tumors diagnosed in children and young adults. These tumors are commonly treated with surgery and/or radiation therapy and combination chemotherapy. However, there is a strong need for the development and utilization of targeted therapeutic methods to improve patient outcomes. Towards accomplishing this goal, pre-clinical models for these unique malignancies are of particular importance to design and test experimental therapeutic strategies prior to being introduced to patients due to their origination site and propensity to metastasize. Pre-clinical models offer several advantages for the study of pediatric sarcomas with unique benefits and shortcomings dependent on the type of model. This review addresses the types of pre-clinical models available for the study of pediatric solid tumors, with special attention to the bone sarcomas osteosarcoma and Ewing sarcoma.

Keywords: Ewing sarcoma; bone sarcomas; cancer therapy; osteosarcoma; pediatric cancer; preclinical models; rare cancer; solid tumors.

Figure 1

Common in vitro cell lines and in vivo animal models of osteosarcoma. Commonly used cell lines, including their genomic characteristics (26, 27), and in vivo animal models (–30) are listed for osteosarcoma.

Figure 2

Common in vitro cell lines and in vivo animal models of Ewing sarcoma. Commonly used cell lines, including their fusion type (31) and genomic characteristics (–36), and in vivo animal models (–42) are listed for Ewing sarcoma.

Figure 3

Animal models of osteosarcoma and Ewing sarcoma. Osteosarcoma (shown on the left) is often modeled using genetically modified murine models (GEMMs) [adapted from (135)] and patient-derived xenografts (PDXs) implanted in immunodeficient mice. Additionally, canine osteosarcoma closely resembles the human disease, providing insights into potential therapeutic options for human osteosarcoma. For Ewing sarcoma (shown on the right), in vivo pre-clinical models include PDXs or transgenic models such as Drosophila melanogaster [adapted from (42)] or zebrafish [adapted from (136)].