# Mouse Models of Osteosarcoma: Unraveling Disease Mechanisms and Accelerating Drug Discovery and Development

**Authors:** Staci L. Haney, Sarah A. Holstein

PMC · DOI: 10.1002/cnr2.70390 · 2025-10-31

## TL;DR

This review discusses how mouse models help study osteosarcoma biology and test new treatments, aiming to improve outcomes for patients.

## Contribution

The paper reviews the strengths and limitations of various mouse models for osteosarcoma and their role in drug development.

## Key findings

- Mouse models have enabled testing of nanoparticle drug delivery systems for osteosarcoma.
- Preclinical studies using mouse models have advanced immunotherapies for osteosarcoma.
- The paper evaluates different types of mouse models used in osteosarcoma research.

## Abstract

Osteosarcoma is the most frequent primary bone malignancy, affecting mainly children, adolescents, and young adults. For the past 40 years, improvements in the survival of patients with osteosarcoma have been minimal, primarily as a consequence of the lack of systemic therapy options beyond traditional cytotoxic agents. In particular, management of metastatic and recurrent disease continues to be a significant clinical challenge.

Mouse models of osteosarcoma serve as a valuable tool to study disease biology, metastasis, and response to novel treatments. In recent years, mouse models have been employed to evaluate the efficacy of several innovative drugs, including nanoparticle formulations that can target drug delivery to osteosarcoma tumor cells and diminish off‐target effects. In addition, significant preclinical advancements in immune checkpoint inhibitors and immunotherapies for osteosarcoma have been made with the aid of mouse models.

This review provides insight into the advantages and shortcomings of the numerous osteosarcoma mouse models described in the literature, including transgenic, orthotopic, and heterotopic models as well as patient‐derived xenografts. We highlight how these models are currently being used to support preclinical studies focused on the development of novel therapies.

## Linked entities

- **Diseases:** osteosarcoma (MONDO:0002623)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** bone malignancy (MESH:D001859), metastasis (MESH:D009362), Osteosarcoma (MESH:D012516)
- **Chemicals:** cytotoxic (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]

## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12576592/full.md

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Source: https://tomesphere.com/paper/PMC12576592