Tumor-permissive Collagen Signatures in Canine Mammary Gland Tumors: Development of Prognostic Markers and Targeted Therapies for Improved Outcomes
Mammary gland tumors (MGT) are the most common malignancies in intact female dogs, and the resulting premature death and morbidity in this sub-population of dogs represents a significant health problem. While genetic alterations within tumor cells can promote their uncontrolled growth and ability to spread to distant sites, recent work indicates that normal, non-malignant cells and extracellular matrix (ECM) within the surrounding tumor stroma also regulate the growth and spread of cancer. The investigators have identified cancer-associated stromal (collagen) signatures in canine MGT biopsy samples that predict clinical outcome better than commonly used markers. These predictive markers may improve the veterinary oncologist’s ability to accurately predict which dogs truly need aggressive treatment from those that do not. Notably, their laboratories have shown that inhibition of a collagen-degrading enzyme (Fibroblast Activation Protein (FAP)) and increasing a tumor suppressive collagen (type III collagen (Col3)) prevent the formation of these tumor-inciting signatures in other species (mouse and human). This work suggests that if these novel targets can suppress tumor-permissive collagen signatures in the dog, we can treat canine MGT more effectively. The goals of this project are 1) to identify additional collagen signatures which predict clinical outcome in dogs, 2) determine how they direct tumor cell behavior and 3) develop therapies that prevent formation of tumor-inciting collagen signatures in canine MGT. Based on the investigators’ published and preliminary data, they predict that identifying and targeting tumor-inciting collagen signatures will lead to improvements in both diagnosis and treatment of dogs with malignant MGT.
Co-sponsored with the AKC Canine Health Foundation, Grant Number: 02489
University of Pennsylvania