Bailey Roberts, MD - Best of the Best in Pediatric Surgery 2024
With Dr. Bailey Roberts & Dr. Bailey Roberts · Live Event Content
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Educational content from recorded physician discussions — not medical advice. Talk to your (or your child's) care team about your situation.
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What the experts said
Osteosarcoma most commonly affects adolescents and young adults
Gross metastasis at the time of diagnosis is present about 20% of the time in osteosarcoma
The most common site of metastasis in osteosarcoma is in the lung
Overall survival in osteosarcoma worsens from 80% to about 20% for metastatic disease
Recurrence is very common in osteosarcoma, and the most common site of recurrence is in the lungs
Extracellular vesicles are carriers of amino acids, proteins, mRNA or other forms of cellular communication
EV content is unique and specific to the cells that released it, and therefore can be traced back to the cell type
EVs are involved in the metastatic cascade and implicated as potential markers for disease diagnosis and staging
EVs have been shown to change fibroblasts, inhibit T cell activity, and are involved in establishing a pre-metastatic niche
K12 is a spontaneous osteosarcoma with low metastatic capability
K7M2 is a highly metastatic osteosarcoma derived from a spontaneous osteosarcoma that went through two reiterations of harvesting spontaneous lung metastases and reimplanting them into the mouse
The K7M2 cell line is more aggressive and causes death at a much higher rate than K12
Pre-education with K7M2 EVs drastically increases the metastatic burden in the lungs of mice with K7M2 tumors
Pre-education with K7M2 EVs increased the overall mortality during the five-week study period in mice with K7M2 tumors
K7M2 EV education led to increased metastatic burden in mice with K12 tumors
Pre-education with highly metastatic cell line EVs increases the metastasis seen in a normally low metastatic tumor
No mice with K12 tumors died in the study period
Extracellular vesicles delivered prior to tumor implantation from highly metastatic K7M2 increase the metastatic burden of K7M2 tumors
Increased metastatic burden from extracellular vesicles decreases overall survival
Extracellular vesicles from highly metastatic K7M2 increase the metastatic burden of less metastatic K12 tumors
All cells in the body release EVs, so we can't just generally target EVs and hope to decrease the establishment of a pre-metastatic niche
IRF5 is a molecule being explored as a potential immunotherapy target in osteosarcoma EVs
Surgically removing the primary tumor is the current standard of care for osteosarcoma
There are certain membrane EV markers, but they're shared by all types of EVs
The differences in EVs by cell type have more to do with the contents inside of them than the targets on them, which makes them difficult to target as far as treatment
Studies in dogs have shown ability to take serum of dogs with osteosarcoma and determine their likelihood of metastasis based on the EVs