Osteosarcoma is an uncommon and highly aggressive primary malignant bone tumor that differs from other tumors due to the production of an osteoid matrix by the neoplastic cells. Protheragen is a leading provider of preclinical services for osteosarcoma due to its extensive experience in the field of drug development and discovery. At Protheragen, we aim to speed up the conversion of significant research findings into realistic therapeutic options.
Overview of Osteosarcoma
Predominantly affecting children and young adolescents, osteosarcoma is associated with the highest incidence rate of primary malignant bone tumors. It arises from mesenchymal stem cells and is marked by the production of osteoid, which is an immature form of bone. The tumor is commonly found in the femurs, as well as the metaphyseal regions of the fibula and tibia. With an incidence rate of approximately 3-5 cases per annum globally, osteosarcoma has cemented itself as the second leading cause of death in the 10-20 age bracket. Even with this low prevalence, the disability and mortality rates associated with osteosarcoma are alarming, which underscores the need for improved diagnostics and therapeutic options.
Fig.1 The components in the immune microenvironment of osteosarcoma and the mechanisms of their protumor and antitumor effects. (Tian H.,
et al., 2023)
Pathogenesis of Osteosarcoma
The development of osteosarcoma involves a complex interplay of genetics, epigenetics, and external environmental influences. Changes in suppressor genes like TP53 and RB1, which are commonly mutated, lead to cell growth that is unregulated and avoids programmed cell death. Changes to genes that do not affect the DNA sequence, like abnormal DNA methylation and histone changes, contribute to the expression of genes by altering the ways in which genes are turned on and off. Exposure to radiation or the use of certain chemicals is known to increase the risk of developing osteosarcoma. Further, osteosarcoma is potentially initiated by mechanical strain alongside the rapid bone growth seen in adolescence.
Diagnostics Development for Osteosarcoma
Histopathological Examination
Histopathological examination remains a cornerstone in the diagnosis of osteosarcoma. Biopsy samples are analyzed under a microscope to identify the presence of osteosarcoma cells and assess tumor grade. This method provides detailed information on cellular morphology and tissue architecture, aiding in accurate diagnosis.
Immunohistochemistry (IHC)
Immunohistochemistry is a powerful tool used to detect specific proteins in tissue samples. Markers such as osteocalcin, osteopontin, and S100 protein are commonly used to confirm the diagnosis of osteosarcoma and differentiate it from other bone tumors. IHC enhances diagnostic accuracy by providing molecular-level insights.
Molecular Diagnostics
Molecular diagnostics, including next-generation sequencing (NGS), are increasingly used to identify specific genetic mutations and alterations in osteosarcoma. These techniques provide comprehensive genomic profiling, which can guide personalized therapeutic strategies by identifying actionable mutations.
Therapeutics Development for Osteosarcoma
- Chemotherapy
Chemotherapy remains a mainstay in the therapeutic of osteosarcoma, with drugs such as doxorubicin, cisplatin, and methotrexate used in combination regimens. These agents target rapidly dividing cells, reducing tumor size and preventing metastasis. Despite significant improvements in localized disease, metastatic or recurrent osteosarcoma remains challenging to treat.
- Targeted Therapy
Targeted therapies, including small molecule inhibitors, are being developed to address specific molecular pathways involved in osteosarcoma. Anti-angiogenic drugs such as sorafenib and regorafenib inhibit tumor growth and metastasis by targeting angiogenesis. While these therapies show promise, they often face limitations in achieving sustained clinical responses.
- Immunotherapy
Immunotherapy represents a promising frontier in osteosarcoma therapeutics. Immune checkpoint inhibitors, such as anti-PD-1/PD-L1 antibodies, and CAR-T cell therapies are being explored to harness the immune system to attack osteosarcoma cells. Dendritic cell vaccines are also under investigation to enhance the body's natural immune response against the tumor.
Table 1. Summary of clinical trials of immune checkpoint inhibitors (ICIs) in osteosarcoma. (Yu S., et al., 2024)
| Registration NO |
Participant Group |
Target |
Clinical Trial |
Stage |
| NCT03013127 |
Pembrolizumab |
PD−1 |
Pembrolizumab in Patients with Relapsed or Metastatic Osteosarcoma Not Eligible for Curative Surgery |
Phase 2 |
| NCT03006848 |
Avelumab |
PD-L1 |
Avelumab in Patients with Recurrent or Progressive Osteosarcoma |
Phase 2 |
| NCT04668300 |
Oleclumab+Durvalumab |
PD-L1
CD73 |
Oleclumab and Durvalumab in Patients with Recurrent, Refractory, or Metastatic Sarcoma |
Phase 2 |
| NCT02301039 |
Pembrolizumab |
PD−1 |
Pembrolizumab in Patients with Advanced Sarcomas |
Phase 2 |
| NCT02982486 |
Nivolumab+Ipilimumab |
PD−1
CTLA−4 |
Nivolumab Plus Ipilimumab in Patients with Non-resectable Sarcoma and Endometrial Carcinoma |
Phase 2 |
| NCT02406781 |
Pembrolizumab+Metronomic Cyclophosphamide |
PD−1 |
MK3475 and Metronomic Cyclophosphamide in Patients with Advanced Sarcomas |
Phase 2 |
| NCT03359018 |
Apatinib+SHR−1210 |
PD-L1
VEGFR |
Apatinib Plus Anti-PD1 Therapy in Patients with Advanced Osteosarcoma |
Phase 2 |
| NCT02982941 |
Enoblituzumab |
B7-H3 |
Enoblituzumab in Children with B7-H3-expressing Solid Tumors |
Phase 1 |
| NCT03006848 |
Avelumab |
PD-L1 |
Avelumab in Patients with Recurrent or Progressive Osteosarcoma |
Phase 2 |
| NCT02541604 |
Atezolizumab |
PD-L1 |
Atezolizumab in Pediatric and Young Adult Participants with Solid Tumors |
Phase 1/2 |
| NCT03449108 |
Autologous Tumor Infiltrating Lymphocytes+Nivolumab+pilimumab |
PD−1
CTLA−4 |
LN−145 or LN−145-S1 in Treating Patients with Relapsed or Refractory Ovarian Cancer, Triple Negative Breast Cancer (TNBC), Anaplastic Thyroid Cancer, Osteosarcoma, or Other Bone and Soft Tissue Sarcomas |
Phase 2 |
| NCT03676985 |
ZKAB001 |
PD-L1 |
PD-L1 Antibody in Limited Stage of High-grade Osteosarcoma |
Phase 1/2 |
| NCT04359550 |
ZKAB001 |
PD-L1 |
ZKAB001 for Maintenance Therapy in Patients with High-grade Osteosarcoma After Adjuvant Chemotherapy |
Phase 3 |
| NCT04803877 |
Nivolumab+Regorafenib |
PD−1
VEGFR1/VEGFR2/VEGFR3/PDG
FR-β/Kit/RET/Raf−1 |
Regorafenib and Nivolumab in Osteosarcoma |
Phase 2 |
| NCT05182164 |
Pembrolizumab+Cabozantinib |
PD−1
VEGFR2/MET |
Pembrolizumab and Cabozantinib in Patients with Advanced Sarcomas |
Phase 2 |
| NCT03282344 |
NKTR−214+Nivolumab |
PD−1
CD122 |
NKTR−214 in Combination with Nivolumab in Patients with Metastatic and/or Locally Advanced Sarcoma |
Phase 2 |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen provides a full spectrum of diagnostics and therapeutics development services for osteosarcoma. Our offerings include histopathological analysis, immunohistochemistry, molecular diagnostics, and state-of-the-art imaging techniques to deliver precise and comprehensive diagnostic insights. Furthermore, we specialize in the development of targeted therapies, immunotherapies, and gene-based therapies, utilizing advanced research capabilities to enhance therapeutic options for osteosarcoma.
Protheragen's advantage lies in our multidisciplinary approach and commitment to scientific excellence. Our team of experts brings together diverse expertise in pathology, molecular biology, and clinical research, ensuring that each project benefits from a comprehensive and integrated perspective. If you are interested in our services, please feel free to contact us.
References
- Tian, Hailong, et al. "Managing the immune microenvironment of osteosarcoma: the outlook for osteosarcoma treatment." Bone Research 11.1 (2023): 11.
- Yu, Shengnan, and Xudong Yao. "Advances on immunotherapy for osteosarcoma." Molecular cancer 23.1 (2024): 192.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.
