Abstract P2-06-16: New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway

Abstract

Abstract BACKGROUND:Triple negative breast cancer (TNBC) has poor prognosis, lack of targeted therapies and are often refractory to conventional chemotherapy treatments. Therefore, finding new therapeutic targets for those tumours is an unmet need with high clinical impact. In this context, Oncostatin M receptor (OSMR) is a promising therapeutic target as it is over-expressed in this tumour subtype and its activation promotes invasiveness (Guo L, et al. 2013 Oncogene; West NR, et al.2014 Oncogene). We previously showed that OSMR is frequently copy-number gained and over-expressed in squamous cell carcinoma, where it induces migration, invasion and metastasis (Caffarel MM, et al 2013 Journal of Pathology; Caffarel MM, et al 2014 Journal of Pathology; Kucia-Tran JA, et al. 2016 Brit J Cancer; Kucia-Tran JA, et al 2018 Journal of Pathology). We now investigate the role of OSMR in breast cancer progression. METHODS: To address this issue we use a wide array of tools including in vitro cell cultures and in vivo models. The expression of OSMR pathway was analysed in FFPE samples and large datasets of publicly available breast cancer samples (METABRIC, n=1462; and TCGA, n=547). RESULTS: OSMR and its ligand Oncostatin M (OSM) are over-expressed in basal tumours, where they associate with shorter overall survival (p=0.015). While OSMR is expressed by breast cancer cells and cancer associated fibroblasts, the main source of OSM seems to be primarily macrophages. OSM treatment of breast cancer cells induces the expression of important mediators of angiogenesis and invasion. Importantly, OSMR activation accelerates tumour onset, tumour growth and metastasis in orthotopic xenografts in nude mice. CONCLUSIONS: Our results support that OSMR pathway may have an important role in the initiation and progression of breast cancer and that it could be a promising candidate for therapeutic targeting in TNBC. OSMR could be blocked by antibody based inhibition, strategy that has had a major impact on breast cancer. Citation Format: Alvarez I, Araujo A, Abaurrea A, Rezola R, Urruticoechea A, Lawrie C, Caffarel MM. New targets in triple negative breast cancer: Role of Oncostatin M receptor pathway [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-06-16.