Rhabdomyosarcoma (RMS)
Rhabdomyosarcoma (RMS) is an extremely aggressive form of soft tissue sarcoma that predominantly affects children. Our company, a renowned authority in the field of disease drug development and therapy advancement, provides comprehensive services encompassing RMS diagnostics, therapy development, and preclinical research.
Overview of Rhabdomyosarcoma (RMS)
Rhabdomyosarcoma (RMS) is a malignant tumor that originates from immature muscle cells known as rhabdomyoblasts. These tumors can manifest in various regions of the body, including the head and neck, genitourinary tract, extremities, and trunk. RMS is characterized by uncontrolled proliferation and invasion into nearby tissues, resulting in significant morbidity and mortality among affected children. In the United States, the incidence of RMS is approximately 4.71 per million children and adolescents below the age of 20.
Genetic Mutations in Rhabdomyosarcoma (RMS)
Genetic mutations play a crucial role in the development and progression of RMS. Recent studies have identified specific gene alterations that are associated with RMS tumors. For instance, the fusion of the FOXO1 gene with various partner genes, such as PAX3 or PAX7, is a defining genetic abnormality in a subset of RMS cases. This fusion event leads to dysregulated expression of genes involved in muscle development and differentiation.
In addition to FOXO1 fusions, other genetic mutations have been observed in RMS tumors. These include mutations in genes such as BCOR, CDK4, MYCN, NF1, TP53, PIK3CA, RAS isoforms (NRAS, KRAS, HRAS), and others. These mutations contribute to the dysregulation of key signaling pathways involved in cell growth, proliferation, and differentiation.
Fig. 1 Genetic mutations in Rhabdomyosarcoma (RMS). (Shern, Jack F., et al., 2021)Targets of Rhabdomyosarcoma (RMS) Therapy
CDK4
Amplification of the CDK4 gene is frequently observed in RMS tumors. CDK4 inhibitors are being investigated as potential therapeutic agents to inhibit tumor growth.
MYCN
Amplification of the MYCN gene is associated with poor prognosis in RMS. Targeting MYCN signaling pathways may offer new therapeutic opportunities.
RAS isoforms
Mutations in RAS isoforms, particularly NRAS, KRAS, and HRAS, are common in RMS. Inhibitors targeting RAS signaling pathways are being explored for their therapeutic potential.
PI3K-AKT-mTOR pathway
Dysregulation of the PI3K-AKT-mTOR pathway is frequently observed in RMS. Inhibitors targeting this pathway show promise in preclinical studies.
Therapies of Rhabdomyosarcoma (RMS)
- Targeted Therapies
Targeted therapies aim to disrupt the aberrant signaling pathways driving tumor growth and progression. Combinations of different therapy modalities, such as targeted therapies with chemotherapy or radiation therapy, are being explored to improve therapy efficacy and overcome resistance mechanisms.
- Immunotherapies
The immune system plays a critical role in cancer surveillance and elimination. Immunotherapeutic approaches, such as immune checkpoint inhibitors and adoptive T-cell therapies, are being investigated in RMS to enhance the immune response against tumor cells.
| Therapeutic Agents for Rhabdomyosarcoma (RMS) | ||||
| Abemaciclib | Temsirolimus | Cixutumumab | Temozolomide | Bevacizumab |
| Trabectedin | Crizotinib | Onivyde | Talazoparib | Vinorelbine |
| Palbociclib | Pazopanib | Regorafenib | Sorafenib | |
Our Services
Our company offers a comprehensive range of diagnostics and therapy development services for RMS. These services include genetic testing, biomarker analysis, and preclinical research.
Therapy Development Platforms
Animal Models of Rhabdomyosarcoma (RMS)
RMS animal models are invaluable tools for evaluating potential therapies. Our company offers a wide range of services in RMS animal model development.
| Non-Genetically Engineering Model Development | |
| Environmental factors are thought to contribute to the development of RMS. Our company offers environmental-induced model development services to investigate the effects of these factors on tumor formation and progression. We can expose animal models to various environmental agents, such as radiation or chemical carcinogens, to induce RMS-like tumors. | |
| Optional Inducers | Cobalt, Nickel, Pyrrolizidine alkaloid, Benzenediazonium sulphate (BD) |
| Genetic Engineering Model Development | |
| By using advanced gene editing techniques such as CRISPR/Cas9, we can precisely manipulate the genes involved in RMS development and progression. For example, we can introduce the FOXO1 fusion gene, a hallmark of certain RMS subtypes, into mouse models to mimic the genetic alterations observed in human RMS tumors. | |
| Xenograft Model Development | |
| We work with a diverse range of RMS cell lines, each representing different subtypes and genetic alterations observed in human RMS tumors. By injecting these cell lines into mice, we can establish RMS xenografts that closely resemble the characteristics of the original tumors. By using surgically resected or biopsy-derived tumor samples, we can establish PDX models that retain the genetic and histological features of the original tumors. |
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| Optional Species | Mouse, Rat, Zebrafish, 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
- Shern, Jack F., et al. "Genomic classification and clinical outcome in rhabdomyosarcoma: a report from an international consortium." Journal of Clinical Oncology 39.26 (2021): 2859.
- Zarrabi, Ali, et al. "Rhabdomyosarcoma: current therapy, challenges, and future approaches to treatment strategies." Cancers 15.21 (2023): 5269.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.