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Areas of Interest

                                              DESMOID TUMORS

Desmoid tumors are a rare, non-metastasizing, fibrous sarcoma with currently no approved drug therapy. While they can occur in the setting of a congenital syndrome known as familial adenomatous polyposis, the majority arise spontaneously. Depending upon anatomic location, desmoid tumors can cause significant quality of life impairment, including pain, decrease in functional use of limbs and discomfort. As they tend to occur in younger people, the burden of the disease can be felt for decades. Surgical resection is carried out when feasible but recurrence rates are high and associated with morbidity. For surgically unresectable or recurrent disease that needs treatment, oncologists have historically tried a variety of systemic therapies including cytotoxic chemotherapies, tyrosine kinase inhibitors and hormonal antagonists. However, all of these approaches are based on small case series with variable outcomes and none have a clear rationale in the biology of the disease. This is clearly an area of unmet need.
The underlying biology of desmoid tumors is now well understood. The predominant feature of desmoid tumors is increased nuclear beta catenin levels.

OSTEOSARCOMA

Osteosarcoma is the most common cancer of the bone. Most osteosarcomas occur in children and young adults, but osteosarcoma can occur at any age. The canonical Wnt pathway is required for bone cell differentiation and beta catenin is required for bone formation and regulation of bone cells. Beta catenin is present at higher levels in osteosarcoma as it progresses and has been known to regulate metastases to the lungs. Furthermore, Wnt/beta catenin contributes to osteosarcoma’s resistance to chemotherapy. Our current understanding of Wnt/beta catenin’s role in osteosarcoma implicates the loss of an important tumor suppressor, NKD2, as mediating stabilization of beta catenin in the cytoplasm. In turn, the beta catenin protein is not degraded and is free to transport into the nucleus to initiate oncogenic gene expression. Tegavivint has exhibited highly promising results in osteosarcoma animal models, not only with regard to primary tumor inhibition, but also toward inhibition of metastases. Beta Cat has initiated a canine osteosarcoma trial to evaluate the opportunity in a larger species where the disease is very similar to human disease and learn more about Tegavivint’s potential in treating human osteosarcoma.

The study is currently enrolling in Phoenix, Arizona at the Midwestern University Veterinary School.

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