Toward a drug development path that targets metastatic progression in osteosarcoma

Area of Science:

• Oncology
• Translational Medicine
• Cancer Metastasis Research

Background:

• Pulmonary metastasis remains the primary cause of mortality in osteosarcoma patients, despite successful primary tumor treatment.
• Conventional drug development has failed to improve outcomes for osteosarcoma patients in over three decades.
• A deeper understanding of metastasis biology necessitates a shift towards therapeutics targeting metastatic progression.

Purpose of the Study:

• To establish a preclinical translational path for evaluating therapeutics targeting the metastatic phenotype in osteosarcoma.
• To provide a consensus perspective from key opinion leaders on advancing metastasis-specific drug development.
• To address the unmet need for effective treatments targeting cancer spread, applicable beyond osteosarcoma.

Main Methods:

• Convened a meeting of experts in metastasis and osteosarcoma research.
• Focused on identifying metastasis-specific targets and processes.
• Defined requirements for rigorous preclinical data to support clinical translation.

Main Results:

• Confirmed that metastasis-specific targets and processes exist and can be targeted.
• Emphasized the feasibility of developing therapeutics that target metastatic progression.
• Highlighted the need for comprehensive preclinical data, including mechanism of action and pharmacodynamic markers.

Conclusions:

• Therapeutics targeting metastasis-specific processes are feasible and essential for osteosarcoma treatment.
• Rigorous preclinical evaluation in multiple models, including naturally occurring canine osteosarcoma, is critical for drug development.
• A paradigm shift towards targeting metastatic progression is necessary for improving patient survival in osteosarcoma and other cancers.