Cowden syndrome is a hereditary condition that entails the appearance of numerous hamartomatous benign tumors as well as a heightened predisposition to certain malignancies, most noteworthy being colorectal cancer. At Protheragen, we provide a complete range of preclinical drug discovery and development services to transform diagnostic and therapeutic concepts into viable solutions and address the challenging aspects of Cowden syndrome.

Overview of Cowden Syndrome

The frequency of incidence of Cowden syndrome is approximately one in two hundred thousand. Cowden syndrome is known to have polyposis hamartomatous in which polyps can form in practically any organ. Over time, evidence of digestive tract involvement has grown, resulting in the inclusion of gastrointestinal manifestations (multiple hamartomas, glycogenic acanthosis, and colorectal cancer) into the diagnostic criteria. Mixed histology polyps are common, and hamartomas and ganglioneuromas predominate.

Fig.1 Microscopic pathology of Cowden syndrome individuals. (Zhao, M., et al., 2022)

Pathogenesis of Cowden Syndrome

Cowden syndrome is an uncommon condition characterized by an autosomal dominant mutation of the tumor suppressor gene, PTEN, located on chromosome 10q22-23. Recent studies indicate that approximately 60% to 90% of the pathogenic variants are familial.

PTEN is a critical component of the signaling pathway that restrains cellular growth by inhibiting the PI3K/AKT/mTOR cascade. Loss of function of PTEN due to mutation results in hyperplasia or overgrowth as a consequence of pathway malfunction. It results in multi-system tissue and cell overgrowth with a wide range of phenotypic manifestations including, but not limited to, benign and malignant tumors, macrocephaly, developmental delay, and skin lesions.

Fig.2 PI3K/AKT/mTOR pathway and PTEN regulation. (Dragoo, D. D., et al., 2021)

Therapeutics Development for Cowden Syndrome

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

To minimize the burden of these rare and intricate diseases, we focus on developing pioneering methods of diagnosing and treating these conditions through the application of modern molecular tools and other novel approaches. Furthermore, we conduct preclinical studies along with disease model development including pharmacokinetic and drug safety testing; this comprehensive approach accelerates the development process, all while increasing the likelihood of regulatory success.

Therapeutic Development Services

• Small Molecule Drug
• Cell Therapy Development
• Gene Therapy Development
• Therapeutic Antibody

• Therapeutic Peptide
• Therapeutic Protein
• Microbiome Therapeutic
• More

Animal Model Development Services for Cowden Syndrome

Animal models serve as a firm structure that connects basic science and application. In our firm, we develop custom animal models for Cowden syndrome. Our specialists harness modern technology and strong scientific knowledge to create, design, and verify animal models that mimic the disease phenotype, to improve the speed of the preclinical phase for drug development and increase the predictive value of outcomes.

Genetically Engineering Model

Animal models for Cowden syndrome are primarily based on manipulating PTEN expression in various organisms.

Optional models: Pten-KO model, Pten-flox model, etc.

At Protheragen, what distinguishes us is our devotion to innovation, quality, and collaboration. We integrate profound scientific knowledge with a focus on the customer to change the arena of research on rare gastrointestinal illnesses. Do not hesitate to reach out to us for further understanding regarding these diseases and the services we provide.

References

• Dragoo, David D et al. "PTEN Hamartoma Tumor Syndrome/Cowden Syndrome: Genomics, Oncogenesis, and Imaging Review for Associated Lesions and Malignancy." Cancers 13.13 (2021): 3120.
• Zhao, Mingkun et al. "Case Report: Duodenal Carcinoma in a 40-Year-Old Asian Man with Cowden Syndrome." Frontiers in surgery 9 (2022): 935048.
• D'Ermo, Giuseppe, and Maurizio Genuardi. "Gastrointestinal manifestations in PTEN hamartoma tumor syndrome." Best practice & research. Clinical gastroenterology 58-59 (2022): 101792.

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