Advancing therapy for osteosarcoma

Gill, Jonathan; Gorlick, Richard

doi:10.1038/s41571-021-00519-8

Cited by 876Sarcoma Diagnosis and TreatmentBone Tumor Diagnosis and TreatmentsOvarian cancer diagnosis and treatment

Advancing therapy for osteosarcoma

Gill, Jonathan, Gorlick, Richard·2021·Nature Reviews Clinical Oncology

DOI 10.1038/s41571-021-00519-8

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Abstract

Improving the survival of patients with osteosarcoma has long proved challenging, although the treatment of this disease is on the precipice of advancement. The increasing feasibility of molecular profiling together with the creation of both robust model systems and large, well-annotated tissue banks has led to an increased understanding of osteosarcoma biology. The historical invariability of survival outcomes and the limited number of agents known to be active in the treatment of this disease facilitate clinical trials designed to identify efficacious novel therapies using small cohorts of patients. In addition, trial designs will increasingly consider the genetic background of the tumour through biomarker-based patient selection, thereby enriching for clinical activity. Indeed, osteosarcoma cells are known to express a number of surface proteins that might be of therapeutic relevance, including B7-H3, GD2 and HER2, which can be targeted using antibody-drug conjugates and/or adoptive cell therapies. In addition, immune-checkpoint inhibition might augment the latter approach by helping to overcome the immunosuppressive tumour microenvironment. In this Review, we provide a brief overview of current osteosarcoma therapy before focusing on the biological insights from the molecular profiling and preclinical modelling studies that have opened new therapeutic opportunities in this disease.

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Patients with radiographically confirmed non-metastatic osteosarcoma have a 5-year event-free survival of approximately 60%.
“Those patients with radiographically confirmed non-metastatic osteosarcoma have a 5-year event-free survival of ~60% 9 .”
From Osteosarcoma (2022) · cites this paper as [9]
Patients with a primary lesion and multiple pulmonary nodules or radiographically detectable metastatic disease at other sites have a 5-year event-free survival below 20%.
“For individuals with a primary lesion and multiple pulmonary nodules or radiographically detectable metastatic disease at other sites, 5-year event-free survival is <20% 9 .”
From Osteosarcoma (2022) · cites this paper as [9]
Approximately 80% of patients with osteosarcoma present with radiographically localized disease.
“Approximately 80% of patients with osteosarcoma present with radiographically localized disease 9 .”
From Osteosarcoma (2022) · cites this paper as [9]
Patients with a primary lesion and an isolated pulmonary nodule have a 5-year event-free survival generally below 40%.
“In patients who present with a primary lesion and an isolated pulmonary nodule, 5-year event-free survival is generally <40% 9 .”
From Osteosarcoma (2022) · cites this paper as [9]
Copy number amplifications of potentially targetable genes seemed to predict sensitivity to specific agents, but subsequent work has shown that the picture is much more complicated.
“Copy number amplifications of potentially targetable genes seemed to predict sensitivity to specific agents 35 ; however, subsequent work has shown that the picture is much more complicated 9 .”
From Osteosarcoma (2022) · cites this paper as [9]

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Osteosarcoma
Beird, H. C., Bielack, S. S., Flanagan, A. M., Gill, J., Heymann, D., Janeway, K. A., Livingston, J. A., Roberts, R. D., Strauss, S. J., & Gorlick, R. (2022) · Nature Reviews Disease Primers · doi:10.1038/s41572-022-00409-y · Cited by 660 · see citing works
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Osteosarcoma Cells Secrete CXCL14 That Activates Integrin α11β1 on Fibroblasts to Form a Lung Metastatic Niche
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Detection and surveillance of circulating tumor cells in osteosarcoma for predicting therapy response and prognosis
Mu, H., Zuo, D., Chen, J., Liu, Z., Wang, Z., Yang, L., Shi, Q., & Hua, Y. (2022) · Cancer Biology & Medicine · doi:10.20892/j.issn.2095-3941.2022.0279 · Cited by 23 · see citing works
Current Insights into the Management of Late Chemotherapy Toxicities in Pediatric Osteosarcoma Patients
Hecker-Nolting, S., Langer, T., Blattmann, C., Kager, L., & Bielack, S. S. (2021) · Cancer Management and Research · doi:10.2147/cmar.s287908 · Cited by 10 · see citing works

Authors: Gill, J., & Gorlick, R.
Affiliations: The University of Texas MD Anderson Cancer Center (US)
Corresponding author: Gorlick, Richard
ORCID: Gill, Jonathan
Gorlick, Richard
Venue: Nature Reviews Clinical Oncology
Publisher: Springer Science and Business Media LLC
Published: 2021-06-15
Volume: 18
Issue: 10
Pages: 609-624
ISSN: 1759-4774 (ISSN-L)
1759-4782
DOI: 10.1038/s41571-021-00519-8
OpenAlex: W3170090128
Cited by: 876
References: 179
Citations by year: 2026: 137 · 2025: 184 · 2024: 237 · 2023: 174 · 2022: 130 · 2021: 13
FWCI: 22.74
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature Reviews Clinical Oncology (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Sarcoma Diagnosis and Treatment
Health Sciences › Medicine › Rheumatology › Bone Tumor Diagnosis and Treatments
Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
Keywords: osteosarcoma, molecular profiling, tumor microenvironment, B7-H3, GD2, HER2, antibody-drug conjugates, adoptive immunotherapy, immune checkpoint blockade, tumor suppressor, biomarker-based patient selection, tumor heterogeneity, preclinical models
MeSH terms: Antibodies, Monoclonal, Bone Neoplasms, Combined Modality Therapy, Humans, Receptors, Antigen, T-Cell, Osteosarcoma, Primary Cell Culture

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