Future directions in the treatment of osteosarcoma
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Updated: Mar 29, 2026
Establishment of Cancer Stem Cell Cultures from Human Conventional Osteosarcoma
Published on: October 14, 2016
Michael W Bishop1, Katherine A Janeway, Richard Gorlick
1aDepartment of Oncology, St. Jude Children's Research Hospital bDepartment of Pediatrics, University of Tennessee Health Science Center, Memphis, Tennessee cDana-Farber Cancer Institute, Boston, Massachusetts dDivision of Pediatric Hematology/Oncology, The Children's Hospital At Montefiore, Bronx, New York, USA.
Purpose Of Review:
Overall survival rates for osteosarcoma have remained essentially unchanged over the past 3 decades despite attempts to improve outcome via dose intensification and modification based on response. This review describes recent findings from contemporary clinical trials, advances in the comprehension of osteosarcoma biology and genomic complexity, and potential opportunities using targeted and immune-mediated therapies.
Recent Findings:
Recent results from international collaborative trials have failed to demonstrate an ability to improve outcomes using a design in which the randomized question is dictated based on histologic response to preoperative chemotherapy. Novel prognostic markers assessable at diagnosis are vital to identifying subsets of osteosarcoma. Clinical trials focus has now shifted to serial phase II studies of novel agents to evaluate for activity in recurrent and refractory disease. In-depth analyses have revealed profound genomic instability and heterogeneity across patients, with nearly universal TP53 aberration. Although driver mutational events have not clearly been established, frequent derangements in specific pathways may suggest opportunities for therapeutic exploitation. Genomic complexity may lend support to a role for immune-mediated therapies.
Summary:
Rigorous preclinical investigations are potentially generating novel strategies for the treatment of osteosarcoma that will inform the next generation of clinical trials, with the opportunity to identify agents that will improve survival outcomes.
Insights
Osteosarcoma survival rates have stalled despite treatment advances. New research explores targeted and immune therapies by analyzing tumor biology and genomic complexity to improve patient outcomes.
Area of Science:
- Oncology
- Genomics
- Translational Medicine
Background:
- Osteosarcoma survival rates have stagnated for 30 years, with limited progress from dose intensification or response-based chemotherapy modifications.
- Current treatment strategies have not significantly improved overall survival in osteosarcoma patients.
- Understanding the biological and genomic complexity of osteosarcoma is crucial for developing novel therapeutic approaches.
Purpose of the Study:
- To review recent findings from clinical trials in osteosarcoma.
- To discuss advances in understanding osteosarcoma biology and genomic complexity.
- To explore potential opportunities for targeted and immune-mediated therapies in osteosarcoma treatment.
Main Methods:
- Analysis of results from international collaborative clinical trials.
- Review of in-depth genomic analyses of osteosarcoma.
- Examination of contemporary clinical trial designs and outcomes.
Main Results:
- International trials using histologic response to chemotherapy have not improved outcomes.
- Osteosarcoma exhibits profound genomic instability and heterogeneity, with near-universal TP53 aberration.
- Focus is shifting to phase II studies of novel agents for recurrent/refractory disease, exploring pathway derangements and immune-mediated therapies.
Conclusions:
- Preclinical research is generating novel strategies for osteosarcoma treatment.
- Next-generation clinical trials will incorporate these findings to improve survival outcomes.
- Targeted and immune-mediated therapies show promise for future osteosarcoma management.
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