Dermatofibrosarcoma Protuberans (DFSP)
Dermatofibrosarcoma protuberans (DFSP) is a rare skin tumor that arises from the dermis. It is characterized by locally aggressive growth and a high propensity for recurrence. Our company is at the forefront of research and development in the field of DFSP, with a focus on advancing therapy and diagnostics development services for this rare disease.
Introduction to Dermatofibrosarcoma Protuberans (DFSP)
Dermatofibrosarcoma protuberans (DFSP) is a rare soft tissue tumor that predominantly affects the skin. The estimated annual incidence of DFSP is 0.8 to 5.0 cases per million. It was first described by Darier and Ferrand in 1924 as a "progressive and recurrent dermatofibroma." DFSP is characterized by a slow-growing, indurated plaque or nodule that can gradually evolve into a protuberant tumor. It typically arises in young to middle-aged adults and has a predilection for the trunk and extremities.
Pathogenesis of Dermatofibrosarcoma Protuberans (DFSP)
The pathogenesis of DFSP is attributed to a specific chromosomal translocation, t(17;22)(q22;q13), resulting in a fusion between the COL1A1 and PDGFB genes. This fusion gene leads to the constitutive activation of PDGFB, a potent mitogen for fibroblasts and myofibroblasts. The continuous stimulation of these cells promotes the uncontrolled growth and invasion seen in DFSP.
Fig. 1 Histopathology of dermatofibrosarcoma protuberans. (Hao X., et al., 2020)Targets of Dermatofibrosarcoma Protuberans (DFSP) Therapy
The fusion protein COL1A1-PDGFB, resulting from the chromosomal translocation, plays a central role in DFSP pathogenesis. It activates PDGFRβ signaling pathways, leading to cell proliferation and survival. Other potential targets include downstream effectors of PDGFRβ, such as MAPK and PI3K/AKT signaling pathways, which regulate cell growth and differentiation.
Rare Variants of Dermatofibrosarcoma Protuberans (DFSP)
Sclerosing DFSP
This variant is characterized by dense sclerotic and hypocellular stroma, with at least 50% of the tumor embedded in such stroma. Differential diagnosis includes lichen sclerosus, morphea, sclerotic fibroma, and sclerosing epithelial fibrosarcoma.
Granular Cell DFSP
This variant shows larger polygonal cells with abundant granular eosinophilic cytoplasm. Differential diagnosis includes granular cell tumor, which can be distinguished through immunohistochemistry studies.
Fibrosarcomatous DFSP
This variant exhibits increased cellularity, atypia, and mitotic activity. It carries a higher risk of recurrence and metastatic potential. Differential diagnosis includes other spindle cell sarcomas, with molecular testing aiding in precise diagnosis.
Targeted Therapy of Dermatofibrosarcoma Protuberans (DFSP)
Targeted therapy has emerged as a promising approach for the therapeutics of DFSP. One of the most notable targeted therapies is Imatinib mesylate (IM), a potent and specific protein tyrosine kinase inhibitor. IM specifically targets and inhibits the phosphorylation and activation of the PDGFRβ, thereby blocking the aberrant signaling pathway responsible for DFSP growth.
In cases of IM resistance, other multikinase inhibitors such as sorafenib, sunitinib, and pazopanib have shown effectiveness. These inhibitors target multiple kinases, including PDGFR and other signaling pathways involved in DFSP growth. Additionally, CDK4/6 inhibitors PD-0332991 and LEE011 have shown potential in inhibiting DFSP proliferation, particularly in p16-negative FS-DFSP.
Our Services
As a leading company in the field of rare disease research, we have developed state-of-the-art diagnostics for DFSP. Our diagnostic assays aim to detect the COL1A1-PDGFB fusion gene, enabling accurate diagnosis and classification of DFSP subtypes. In addition to diagnostics, our company is actively involved in the development of novel therapies for DFSP.
Therapy Development Platforms
Animal Models of Dermatofibrosarcoma Protuberans (DFSP)
Animal models provide a valuable platform for studying the pathogenesis and therapeutic strategies of rare diseases like DFSP. By utilizing animal models, researchers can gain insights into tumor growth, invasion, and response to various therapies.
| Xenograft Model Development | |
| Our experienced team specializes in establishing xenograft models using patient-derived DFSP cell lines. We have successfully developed several DFSP cell lines, including NCC-DFSP5-C1 and NCC-DFSP4-C1, which harbor the COL1A1-PDGFB fusion gene and faithfully recapitulate the key features of DFSP. These cell lines serve as valuable tools for generating xenograft models in immunodeficient mice. | |
| Optional Species | Mouse, Rat, Non-human primates, Others |
Furthermore, we offer a wide range of personalized animal models tailored to meet various requirements. If you are interested in our services, please do not hesitate to contact us for further information and details regarding pricing and related services.
References
- Hao X., et al. "Dermatofibrosarcoma protuberans: update on the diagnosis and treatment." Journal of clinical medicine 9.6 (2020): 1752.
- Trinidad Celestine M., et al. "Rare variants of dermatofibrosarcoma protuberans: clinical, histologic, and molecular features and diagnostic pitfalls." Dermatopathology 10.1 (2023): 54-62.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.