Biomarker- based therapeutic prevention of bone metastases in breast cancer. Defining the pathophysiologic impact of the endosteal niche

• Project Number: LSC18-010
• Project Lead: Sonia Vallet, Karl Landsteiner University of Health Sciences / Molecular Oncology / Hematology, Sonia Vallet, Karl Landsteiner University of Health Sciences / Division of Internal Medicine 2 (University Hospital Krems)
• Project Partner: IMC University of Applied Sciences Krems / Department of Life Sciences
• Duration: 36 months starting from 1 December 2019

Background

Breast cancer (BC) is the most common malignancy in women. Most of the tumors are detected at early stages and treated with curative intent. However, up to one third of patients relapse, of which 70% develop bone metastases with survival rates dropping under 10% at 5 years. Efforts to find markers of bone metastases development have so far failed, mainly due to the poor understanding of early pathogenetic steps. Therefore, there remains a need for biomarkers that identify patients at high risk for bone metastases. In addition, despite the frequency of skeletal involvement and the associated morbidity and mortality, effective strategies to prevent bone metastases are lacking. Previous studies identified the endosteum as site of entry for bone metastatic BC cells, where OBs regulate tumor cell migration and survival. Specifically, our own data suggest a key role for pre-OBs in BC bone colonization. Here, I propose to unravel the pathophysiologic role of the endosteal niche, OB lineage cells in particular, during early phases of BM in BC by generating innovative in vitro models of OB differentiation.