Extramammary Paget Disease (EMPD)

Extramammary Paget's Disease (EMPD) is a rare intraepithelial adenocarcinoma that primarily affects areas with a high density of apocrine glands, such as the anogenital region. This disease presents a significant challenge in treatment due to a high rate of local recurrence and potential for metastasis. Protheragen offers end-to-end preclinical drug and therapy development services that confront the specific challenges posed by Extramammary Paget's Disease.

Introduction to Extramammary Paget Disease

Extramammary Paget disease is considered a rare cutaneous malignancy, a form of adenocarcinoma with an incidence estimated to be 0.1 per 100,000 individuals. It is characterized by slow-growing, red, scaly, and eczematous-appearing lesions that can be easily mistaken for benign dermatoses. The disease is classified as primary when it originates from the skin's epidermal cells, and secondary when it arises from an underlying internal malignancy. The risk of metastasis is a major concern, particularly in cases with dermal invasion, which significantly worsens the prognosis.

Fig.1 Histopathology of secondary extramammary Paget disease of colorectal origin. (Shah et al., 2024)

Pathogenesis of Extramammary Paget Disease

It is widely accepted that extramammary Paget disease originates from the malignant transformation of apocrine gland-associated stem cells in the epidermis. The hallmark feature consists of the intraepidermal proliferation of large, pale-staining Paget cells, which are positive for cytokeratin 7 (CK7). These cells are driven by multiple oncogenic signaling pathways, including HER2/neu, androgen receptors (AR), and the PI3K/AKT/mTOR pathway. Therefore, it is speculated that uncontrolled cellular proliferation and invasion are primarily driven by specific molecular aberrations, making these pathways attractive targets for therapeutic intervention.

Therapeutics Development for Extramammary Paget Disease

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 has the capability to provide complete services to advance the therapy for extramammary Paget disease. Our expert scientists, dermatologists, and geneticists use advanced technology to enable progress in focused therapeutic development and disease model development services to support your initiatives.

Therapeutic Development Platforms for Extramammary Paget Disease

Disease Models Development for Extramammary Paget Disease

Protheragen offers a comprehensive provision of preclinical models to facilitate your EMPD translational applied research with advanced platforms of both 2D cell models, 3D skin models, and animal models development, which are all ready to model the disease-specific pathologies to expedite therapeutic development.

2D Cell Models & 3D Skin Models

• Primary EMPD tumor cells
• Androgen receptor-positive Paget cell lines
• HER2-amplified 3D spheroids
• Apocrine gland differentiation co-cultures
• Multilayered anogenital skin equivalent

Animal Models Development

• Orthotopic EMPD PDX models
• Keratinocyte-specific ERBB2 transgenic mouse
• AR-overexpressing rat model
• Chemical-induced perianal Paget disease swine
• Zebrafish xenograft model

DMPK & Drug Safety Evaluation Services

In Vitro ADME Services

• Metabolic Stability Assay
• Collagen Binding Affinity
• Macrophage Uptake Assay
• Plasma Protein Binding
• Skin Penetration Test

In Vivo Pharmacokinetics Services

• Dermal Distribution Mapping
• Tissue Concentration Analysis
• Lymph Node Retention
• Blood-to-Plasma Ratio
• Metabolite Profiling

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 a one-stop preclinical research services provider, Protheragen is dedicated to advancing therapeutics for  rare skin diseases like extramammary Paget disease. Our end-to-end solutions seamlessly span from target discovery and disease modeling to drug safety evaluation and DMPK services.

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

References

• Shah, R. R., et al. "Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis." J Am Acad Dermatol 91.3 (2024): 409-18.
• Shibuya, M., et al. "Extramammary Paget Disease in the Peristomal Skin of an Ileal Conduit Reconstructed with a Pedicled Anterolateral Thigh Flap." Plast Reconstr Surg Glob Open 13.5 (2025): e6793.

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