Osteosarcoma in the Post Genome Era: Preclinical Models and Approaches to Identify Tractable Therapeutic Targets

Area of Science:

• Oncology
• Translational Research
• Comparative Oncology

Background:

• Osteosarcoma (OS) is the most common bone cancer, yet remains rare.
• Treatment outcomes for OS have seen little improvement over decades.
• Genomic studies have revealed the OS mutational landscape but few direct therapeutic targets.

Purpose of the Study:

• To describe novel preclinical models for osteosarcoma (OS).
• To highlight how these models can identify, test, and prioritize therapeutic candidates.
• To emphasize the utility of cross-species approaches in OS research.

Main Methods:

• Generation of high-fidelity murine models of OS.
• Establishment of patient-derived OS xenografts (PDX).
• Utilizing spontaneous canine OS as a translational model.
• Chemical and genetic screening across models.
• Preclinical therapeutic testing in PDX and canine OS models.

Main Results:

• Developed robust preclinical platforms for OS research.
• Identified potential therapeutic targets with cross-species activity.
• Validated new therapies through clinical trials in PDX and canine OS models.
• Demonstrated the efficacy of integrated target discovery and testing.

Conclusions:

• Preclinical models, including canine OS and PDX, are crucial for advancing OS therapeutics.
• Cross-species platforms facilitate rigorous evaluation and prioritization of novel therapies.
• This approach may accelerate the development of effective treatments for osteosarcoma.
• Improving clinical outcomes in OS remains a critical unmet need.