Establishing the role of Secreted-Frizzled-Related Protein (SFRP1) in metastasis formation in canine patients with mammary tumours

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Mammary tumours are the prevalent neoplasms in female dogs. ~50% of all intact bitches will develop mammary tumours of which half will be malignant, often leading to death through metastasis formation. There are currently no standardised diagnostic or prognostic molecular biomarkers available to guide treatment in dogs. Further, treatment options for mammary carcinomas are mostly limited to surgical removal of the diseased gland(s) as chemotherapy has no proven survival benefit and targeted therapies are not available. There is hence an urgent clinical need for a reliable prognostic biomarker that can guide treatment, and for new effective treatment options. We recently identified secreted frizzled-related protein 1 (SFRP1) as a potential biomarker for risk of tumour progression. SFRP1 was negatively associated with increased risk of metastatic behaviour in two datasets of canine mammary tumours (CMT). As SFRP1 is an antagonist to several cancer associated growth-promoting pathways, including the canonical and non-canonical Wnt- and RANK- pathways, treatment with a drug that could mimic its activity could potentially open up new targeted treatment options in the future. This project aims to firmly establish SFRP1 as a reliable prognostic biomarker to aid in CMT diagnostics, as well as to study the biology underlying the progressive behaviour of CMT due to SFRP1 loss, and thereby identify potential new ways to supress CMT growth and progression.