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Updated: Jul 30, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Molecular mechanisms of osteosarcoma metastasis and possible treatment opportunities
Xinhui Du1,2,3, Hua Wei4, Boya Zhang1,2,3
1Bone Soft Tissue Department, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
Abstract:
In osteosarcoma patients, metastasis of the primary cancer is the leading cause of death. At present, management options to prevent metastasis are limited and non-curative. In this study, we review the current state of knowledge on the molecular mechanisms of metastasis and discuss promising new therapies to combat osteosarcoma metastasis. Genomic and epigenomic changes, metabolic reprogramming, transcription factors, dysregulation of physiologic pathways, and alterations to the tumor microenvironment are some of the changes reportedly involved in the regulation of osteosarcoma metastasis. Key factors within the tumor microenvironment include infiltrating lymphocytes, macrophages, cancer-associated fibroblasts, platelets, and extracellular components such as vesicles, proteins, and other secreted molecules. We conclude by discussing potential osteosarcoma-limiting agents and their clinical studies.
Insights
Osteosarcoma metastasis, a major cause of death, is driven by complex molecular changes. This review explores these mechanisms and discusses novel therapies to prevent cancer spread.
Area of Science:
- Oncology
- Cancer Metastasis Research
Background:
- Metastasis in osteosarcoma is the primary cause of mortality in patients.
- Current therapeutic strategies for preventing osteosarcoma metastasis are limited and often ineffective.
Purpose of the Study:
- To review the molecular mechanisms underlying osteosarcoma metastasis.
- To discuss emerging therapeutic approaches for combating osteosarcoma metastasis.
Main Methods:
- Literature review of genomic, epigenomic, metabolic, and signaling pathway alterations.
- Analysis of the tumor microenvironment's role, including cellular and extracellular components.
- Examination of current clinical studies on potential osteosarcoma-limiting agents.
Main Results:
- Osteosarcoma metastasis involves genomic/epigenomic changes, metabolic reprogramming, transcription factor dysregulation, and pathway alterations.
- The tumor microenvironment, comprising immune cells, fibroblasts, platelets, and extracellular molecules, significantly influences metastasis.
- Several novel therapeutic agents show promise in preclinical and early clinical studies.
Conclusions:
- Understanding the multifaceted molecular drivers of osteosarcoma metastasis is crucial.
- Targeting these molecular mechanisms and the tumor microenvironment offers new therapeutic avenues.
- Further clinical investigation of novel agents is warranted to improve patient outcomes.
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