Undifferentiated Pleomorphic Sarcoma

Undifferentiated pleomorphic sarcoma (UPS) is one of the most aggressive forms of soft tissue sarcoma. It is difficult to treat due to its complex genomic landscape and the absence of a definitive molecular signature. Protheragen leverages its deep understanding of the unique molecular pathology of UPS to drive preclinical research, accelerating the development of innovative therapeutics

Introduction to Undifferentiated Pleomorphic Sarcoma

Undifferentiated pleomorphic sarcoma (UPS) was previously known as malignant fibrous histiocytoma. It is a soft tissue sarcoma that stems from mesenchymal cells and is classified as high-grade. It is one of the "rarer" soft tissue sarcomas and is estimated to account for roughly 5-10% of all adult soft tissue sarcomas, translating to approximately 650-1300 new cases diagnosed each year in the US. The tumor most commonly appears in the deep soft tissues of the extremities, particularly the thighs, and as a mass, it appears progressively painless.

Pathogenesis of Undifferentiated Pleomorphic Sarcoma

The genomic instability witnessed in UPS is more pronounced than in other diseases. Chromosomal structural alterations, which include various chaotic genomic rearrangements within chromatin, generate pathways that are fundamentally disordered. Numerous cellular pathways are perturbed as a result of this. The oncogenic pathways most often affected include to some degree the p53 and retinoblastoma (RB) tumor suppressor pathways as well as the PI3K/AKT/mTOR and MAPK signaling pathways. In addition, UPS is often an "hot" tumor, that is, one which is associated with a strong inflammatory response. The tumor also exhibits a large number of mutations, which, in addition to being an indicator of genomic instability, points to the tumor microenvironment being of central importance to tumor advancement and providing avenues for immunotherapy.

Fig.1 Model summarizing the role of Skp2 and p16 in UPS/MFS. (Sun et al., 2023)

Therapeutics Development for Undifferentiated Pleomorphic Sarcoma

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 complete service to accelerate therapeutic development for rare sarcomas such as undifferentiated pleomorphic sarcoma. Our specialists, including oncologists, pathologists, and geneticists, formulate therapeutic and disease model development services to support all research project phases.

Therapeutic Development Platforms for Undifferentiated Pleomorphic Sarcoma

Disease Model Development for Undifferentiated Pleomorphic Sarcoma

Protheragen excels in developing custom 2D cell models, 3D skin models and animal models that accurately mimic UPS's etiology, characterized by complex genomic instability and high metastatic potential. These models are invaluable for therapeutic testing and validation.

2D Cell Models & 3D Skin Models

• Primary UPS tumor-initiating cells
• Radiation-induced genomic instability lines
• 3D CIN70^high spheroids
• Cancer-associated fibroblast (CAF) co-invasion system
• Hypoxic core sarcoma simulator

Animal Models Development

• Orthotopic UPS PDX models
• P53^-/-; Rb^-/- double KO mouse
• CIN-driven transgenic rat
• Radiation-induced UPS swine
• Zebrafish UPS dissemination model

DMPK & Drug Safety Evaluation Services

In Vitro ADME Services

• Phototoxicity & Photostability Assessment
• Dermal Penetration Analysis
• Metabolic Stability & Metabolite Profiling
• Drug Transporter Interaction

In Vivo Pharmacokinetics Services

• PK Profiling in XP Disease Models
• Skin Tissue Distribution
• Local and Systemic Exposure for Topical Formulations
• PK/PD Correlation Studies

Drug Safety Evaluation

• General Toxicology Evaluation
• Genetic Toxicology Evaluation
• Developmental and Reproductive Toxicity Evaluation

• Immunogenicity and Immunotoxicity Evaluation
• Local Toxicity Evaluation
• Phototoxicity Evaluation

• Tissue Cross-Reactivity Evaluation
• Safety Pharmacology Evaluation
• Toxicokinetic Evaluation

As specialists in cutting-edge preclinical research, Protheragen drives the therapeutic development for rare cutaneous and soft tissue sarcomas, including undifferentiated pleomorphic sarcoma. Our core strength lies in our integrated discovery platforms, innovative proprietary disease models, and comprehensive drug safety evaluation and DMPK services, which collectively facilitate the smooth translation from target validation to IND-enabling studies.

If you are interested in our services, please feel free to contact us.

References

• Liang, Z., et al. "Undifferentiated Pleomorphic Sarcoma of the Pancreas: A Rare Case Report and Literature Review." World J Surg Oncol 20.1 (2022): 55.
• Sun, H., et al. "Current Research and Management of Undifferentiated Pleomorphic Sarcoma/Myofibrosarcoma." Front Genet 14 (2023): 1109491.

All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.