Ewing Sarcoma (ES)
Ewing sarcoma (ES) poses significant challenges as a highly aggressive cancer that predominantly impacts the younger population. Our company is committed to propelling ES drug and therapy development, providing tailored diagnostics and services for therapeutic advancements.
Overview of Ewing Sarcoma (ES)
Ewing sarcoma (ES) is a rare and aggressive form of cancer that primarily affects children, adolescents, and young adults. The peak incidence is between 10 and 15 years of age, with approximately 30% of cases occurring in children under 10 years of age and another 30% in adults over 20 years of age. It is characterized by the development of malignant tumors in the bones or soft tissues, such as muscles and tendons. ES most commonly occurs in the long bones of the body, such as the femur and tibia, but can also affect other bones.
Pathogenesis of Ewing Sarcoma (ES)
The exact cause of Ewing sarcoma remains unknown. However, research suggests that it arises from specific genetic abnormalities involving a chromosomal translocation between the EWSR1 gene and a member of the ETS family of transcription factors, most commonly FLI1. This translocation leads to the fusion of the two genes, resulting in the production of abnormal proteins that drive the development and progression of ES.
Targets of Ewing Sarcoma (ES) Therapy
Various targets have been identified, such as the EWS-FLI1 fusion protein, IGF-1R (Insulin-like Growth Factor 1 Receptor), and components of the Wnt signaling pathway. These targets offer potential avenues for the development of targeted therapies, aimed at disrupting the aberrant signaling pathways driving ES growth and survival.
Fig. 1 Immunosuppression in the Ewing sarcoma tumor microenvironment. (Morales, Erin, et al., 2020)Therapies of Ewing Sarcoma (ES)
- Targeted Therapies
An innovative approach is to use small molecule inhibitors that directly target the EWS-FLI1 fusion protein. By inhibiting the activity of this protein, it interferes with signaling pathways that promote tumor growth and survival. - Cell Therapies
- Adoptive cell therapies, such as chimeric antigen receptor (CAR) T-cell therapy, hold great potential in the development of Ewing sarcoma therapies. CAR-T cells are engineered to recognize and target specific antigens present in cancer cells, including those found in Ewing sarcoma.
- Mesenchymal stem cells (MSC) have unique properties that make them ideal candidates for cell therapy. These cells can home to tumor sites and exert antitumor effects through multiple mechanisms, including secretion of anti-inflammatory and anti-angiogenic factors.
Table1 Novel therapies for metastatic ES. (Hesla A. C., et al., 2021)
| Drug Class | Example Drug | Number |
|---|---|---|
| EWSR1-FLI1 target agents | TK216 RP2D and expansion | n = 15 |
| IGF-1R inhibitors | Ganitumab (added to backbone chemotherapy, metastatic) | n = 150 |
| mTOR | Everolimus (Combination with lenvatinib) | n = 1 |
| Microtubuli inhibitors | Eribulin | |
| CDK4/6 inhibitors | Palbociclib, abemaciclib | |
| PARP inhibitors | Talazoparib (combination with irinotecan and temozolamide) | n = 22 (both arms) |
| Multi-targeted tyrosine kinase inhibitors | Cabozantinib | n = 45 |
| Regorafenib | n = 23 | |
| Pazopanib (combination with irinotecan and temozolamide) | n = 7 |
Our Services
With our expertise and state-of-the-art facilities, we strive to contribute to the development of diagnostics and innovative therapies that will bring us closer to a cure for Ewing sarcoma.
Therapy Development Platforms
Animal Models of Ewing Sarcoma (ES)
Animal models are indispensable tools in Ewing sarcoma research. Our Company is at the forefront of Ewing Sarcoma animal model development, offering specialized services in xenograft model development, genetically engineered mouse ES model development, and humanized model development.
| Xenograft Model Development | |
| Xenograft models involve the transplantation of human Ewing sarcoma cells into immunodeficient mice. Through meticulous selection of appropriate Ewing sarcoma cell lines and careful optimization of transplantation techniques, we can establish robust xenograft models that closely resemble the characteristics of human Ewing Sarcoma tumors. | |
| Genetic Engineering Model Development | |
| Using advanced genetic engineering techniques, we can introduce specific genetic alterations into the mouse genome to mimic the molecular characteristics of Ewing sarcoma. This includes the introduction of the EWS-FLI1 fusion gene, which is the hallmark genetic abnormality in Ewing sarcoma. | |
| Humanized Model Development | |
| Our company specializes in the development of humanized mouse models for Ewing Sarcoma research, using CD34+ human hematopoietic stem cells (HSCs) derived from cord blood. By engrafting CD34+ HSCs into immunodeficient mice, we can reconstitute various human immune cell populations, such as T cells, B cells, and macrophages. | |
| Optional Species | Mouse, Rat, Others |
In addition, we also provide other customized animal models to meet diverse needs. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Morales, Erin, et al. "Role of immunotherapy in Ewing sarcoma." Journal for ImmunoTherapy of Cancer 8.2 (2020).
- Yu, Hongjiu, et al. "Potential approaches to the treatment of Ewing's sarcoma." Oncotarget 8.3 (2017): 5523.
- Hesla, Asle Charles, Andri Papakonstantinou, and Panagiotis Tsagkozis. "Current status of management and outcome for patients with Ewing sarcoma." Cancers 13.6 (2021): 1202.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.