Related Experiment Video
Updated: Dec 12, 2025
Intratibial Osteosarcoma Cell Injection to Generate Orthotopic Osteosarcoma and Lung Metastasis Mouse Models
Published on: October 28, 2021
Genomic Complexity of Osteosarcoma and Its Implication for Preclinical and Clinical Targeted Therapies
Courtney Schott1, Avanthi Tayi Shah1, E Alejandro Sweet-Cordero2
1Department of Pediatrics, Division of Hematology and Oncology, University of California San Francisco, San Francisco, CA, USA.
Abstract:
Osteosarcoma is a genomically complex disease characterized by few recurrent single-nucleotide mutations or in-frame fusions. In contrast, structural alterations, including copy number changes, chromothripsis, kataegis, loss of heterozygosity (LOH), and other large-scale genomic alterations, are frequent and widespread across the osteosarcoma genome. These observed structural alterations lead to activation of oncogenes and loss of tumor suppressors which together contribute to oncogenesis. To date, few targeted therapies for osteosarcoma have been identified. It is likely that effectiveness of targeted therapies will vary greatly in subsets of tumors with distinct key driver events. Model systems which can recapitulate the genetic heterogeneity of this disease are needed to test this hypothesis. One possible approach is to use patient-derived xenograft (PDX) models characterized with regards to their similarity to the human tumor samples from which they were derived. Here we review evidence pointing to the genomic complexity of osteosarcoma and how this is reflected in available model systems. We also review the current state of preclinical testing for targeted therapies using these models.
Insights
Osteosarcoma is a complex cancer driven by large genomic alterations, not simple mutations. Patient-derived xenograft (PDX) models are crucial for testing targeted therapies against this genomic diversity.
Area of Science:
- Oncology
- Genomics
- Cancer Biology
Background:
- Osteosarcoma exhibits significant genomic complexity, primarily driven by structural alterations rather than recurrent point mutations or fusions.
- These structural variations, including copy number changes and loss of heterozygosity (LOH), activate oncogenes and inactivate tumor suppressors, driving cancer development.
- The heterogeneity of osteosarcoma suggests that targeted therapies may have variable efficacy depending on specific genomic drivers.
Purpose of the Study:
- To review the genomic complexity of osteosarcoma.
- To evaluate the utility of patient-derived xenograft (PDX) models in recapitulating this complexity.
- To assess the current landscape of preclinical testing for targeted therapies in osteosarcoma models.
Main Methods:
- Review of existing literature on osteosarcoma genomics.
- Analysis of genomic characterization data from osteosarcoma patient-derived xenograft (PDX) models.
- Survey of preclinical studies testing targeted therapies in osteosarcoma models.
Main Results:
- Osteosarcoma is characterized by widespread structural genomic alterations, including copy number changes, chromothripsis, kataegis, and LOH.
- Patient-derived xenograft (PDX) models reflect the genomic heterogeneity observed in human osteosarcoma tumors.
- Current preclinical testing of targeted therapies in these models is ongoing, highlighting the need for models that accurately represent disease complexity.
Conclusions:
- Understanding the genomic complexity of osteosarcoma is essential for developing effective treatments.
- Patient-derived xenograft (PDX) models are valuable tools for studying osteosarcoma's genomic landscape and testing therapeutic strategies.
- Further research using well-characterized PDX models is needed to guide the development of targeted therapies for specific osteosarcoma subtypes.
Related Concept Videos
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...
03:03mTOR Signaling and Cancer Progression
The mTOR pathway or the...