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

乳腺肿瘤是雌性犬中的常见肿瘤。约50%的完整母犬会发生乳腺肿瘤，其中一半是恶性肿瘤，通常通过转移形成导致死亡。目前没有标准化的诊断或预后分子生物标志物可用于指导犬的治疗。此外，乳腺癌的治疗选择大多限于手术切除病变腺体，因为化疗没有证实的生存益处，并且靶向治疗不可用。因此，临床上迫切需要一种可靠的预后生物标志物，可以指导治疗，并为新的有效的治疗方案。我们最近确定分泌型卷曲相关蛋白1（SFRP 1）作为肿瘤进展风险的潜在生物标志物。在犬乳腺肿瘤（CMT）的两个数据集中，SFRP 1与转移行为风险增加呈负相关。由于SFRP 1是几种癌症相关生长促进途径的拮抗剂，包括经典和非经典的Wnt-和RANK-途径，因此使用能够模拟其活性的药物治疗可能会在未来开辟新的靶向治疗选择。该项目旨在将SFRP 1牢固地确立为一种可靠的预后生物标志物，以帮助CMT诊断，并研究由于SFRP 1丢失导致CMT进行性行为的生物学基础，从而确定抑制CMT生长和进展的潜在新方法。

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.