Pathobiology and Molecular Pathways Implicated in Osteosarcoma Lung Metastasis: A Scoping Review

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Osteosarcoma (OS) is the most common primary bone cancer.
• Lung metastasis is the primary cause of mortality in OS patients.
• Metastasis involves complex tumor cell adaptations, immune modulation, and dormancy.

Purpose of the Study:

• To review overlooked and under-researched pathways in OS metastasis.
• To support existing therapeutic targets and identify novel ones.
• To guide future research in OS metastasis.

Main Methods:

• Scoping review adhering to PRISMA-ScR guidelines.
• Searched MEDLINE, Embase, and Cochrane CENTRAL from 2019 onwards.
• Included 43 reports: 30 in vivo, 8 in vitro, 5 observational studies.

Main Results:

• Tumor cell adaptations like EMT and JAK/STAT/TGF-β signaling drive lung metastasis.
• The tumor microenvironment, including tumor-associated macrophages/neutrophils, facilitates pre-metastatic niche formation.
• Lung dormancy links tumor and immune mechanisms, with inflammatory pathways potentially reversing it.

Conclusions:

• Targeting intracellular signaling and immune pathways can mitigate OS metastasis.
• The dual role of tumor-associated macrophages requires further investigation.
• Integrated approaches and combinatorial therapies are crucial for conclusive outcomes, especially regarding lung dormancy.