ArticleOncotarget2015
Personalized comprehensive molecular profiling of high risk osteosarcoma: Implications and limitations for precision medicine.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 47 citations in OpenAlex.
- Precision oncology in the treatment of patients with bone sarcomas: an up-to-date narrative review.Exploration of targeted anti-tumor therapy · 2026Review
- Review
- Activity of pazopanib inOncoscience · 2023Article
- Pramlintide: A Novel Therapeutic Approach for Osteosarcoma through Metabolic Reprogramming.Cancers · 2022Article
- CD44 Contributes to the Regulation of MDR1 Protein and Doxorubicin Chemoresistance in Osteosarcoma.International journal of molecular sciences · 2022Article
- Article
- Protein tyrosine phosphatases in skeletal development and diseases.Bone research · 2022Review
- Bevacizumab, With Sorafenib and Cyclophosphamide Provides Clinical Benefit for Recurrent or Refractory Osseous Sarcomas in Children and Young Adults.Frontiers in oncology · 2022Article
- Receptor tyrosine kinase inhibitors for the treatment of osteosarcoma and Ewing sarcoma.Pediatric blood & cancer · 2021Review
- Pursuing Precision: Receptor Tyrosine Kinase Inhibitors for Treatment of Pediatric Solid Tumors.Cancers · 2021Review
- Review
- Review
- Review
- PLK2 modulation of enriched TAp73 affects osteogenic differentiation and prognosis in human osteosarcoma.Cancer medicine · 2020Article
- [Osteoid-forming bone tumors : Morphology and current translational cell biology].Der Pathologe · 2020Review
- Management of Refractory Pediatric Sarcoma: Current Challenges and Future Prospects.OncoTargets and therapy · 2020Review
- Anticancer Effects of Constituents of Herbs Targeting Osteosarcoma.Chinese journal of integrative medicine · 2019Review
- Alpha Particle Radium 223 Dichloride in High-risk Osteosarcoma: A Phase I Dose Escalation Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Integration of genomic copy number variations and chemotherapy-response biomarkers in pediatric sarcoma.BMC medical genomics · 2019Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDespite advances in molecular medicine over recent decades, there has been little advancement in the treatment of osteosarcoma. We performed comprehensive molecular profiling in two cases of metastatic and chemotherapy-refractory osteosarcoma to guide molecularly targeted therapy. PATIENTS AND
methodsHybridization capture of >300 cancer-related genes plus introns from 28 genes often rearranged or altered in cancer was applied to >50 ng of DNA extracted from tumor samples from two patients with recurrent, metastatic osteosarcoma. The DNA from each sample was sequenced to high, uniform coverage. Immunohistochemical probes and morphoproteomics analysis were performed, in addition to fluorescence in situ hybridization. All analyses were performed in CLIA-certified laboratories. Molecularly targeted therapy based on the resulting profiles was offered to the patients. Biomedical analytics were performed using QIAGEN's Ingenuity® Pathway Analysis.
resultsIn Patient #1, comprehensive next-generation exome sequencing showed MET amplification, PIK3CA mutation, CCNE1 amplification, and PTPRD mutation. Immunohistochemistry-based morphoproteomic analysis revealed c-Met expression [(p)-c-Met (Tyr1234/1235)] and activation of mTOR/AKT pathway [IGF-1R (Tyr1165/1166), p-mTOR [Ser2448], p-Akt (Ser473)] and expression of SPARC and COX2. Targeted therapy was administered to match the P1K3CA, c-MET, and SPARC and COX2 aberrations with sirolimus+ crizotinib and abraxane+ celecoxib. In Patient #2, aberrations included NF2 loss in exons 2-16, PDGFRα amplification, and TP53 mutation. This patient was enrolled on a clinical trial combining targeted agents temsirolimus, sorafenib and bevacizumab, to match NF2, PDGFRα and TP53 aberrations. Both the patients did not benefit from matched therapy.
conclusionsRelapsed osteosarcoma is characterized by complex signaling and drug resistance pathways. Comprehensive molecular profiling holds great promise for tailoring personalized therapies for cancer. Methods for such profiling are evolving and need to be refined to better assist clinicians in making treatment decisions based on the large amount of data that results from this type of testing. Further research in this area is warranted.
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