Cancer-Osteocyte NeTwoRk Atlas

Metastatic breast cancer claims the lives of more European women than any other cancer, and is an ever-growing problem in an aging global population that increasingly survives treatment of primary cancer. The most common site for metastatic breast lesions is bone, with 75% of patients experiencing pathological fractures, spinal cord compression or severe bone pain. Crosstalk between cancer cells and osteocytes, which make up more than 90% of our bone cells and form a complex sensing and signalling network throughout our bones, has recently been implicated in this process. As we now know that breast cancer cells are already present in the bone marrow by the time a primary tumour has been diagnosed, preventing growth of the metastatic colony is the most likely target for successful therapeutic development. A number of molecular mechanisms have been proposed, including by my team, to underly the hijacking of osteocyte signalling by breast cancer cells, but as the osteocyte network is buried deep within hard mineralised tissue, mapping signalling and sensation within it has eluded researchers for decades. CONTRA proposes to embark upon frontier research to provide a greater understanding of the key signalling underlying metastatic bone disease, using cutting-edge techniques to map the osteocyte networks at the tumour-bone interface at single-cell resolution for the first time. I will leverage my expertise in cancer-osteocyte crosstalk, and in vivo, in vitro and in silico modelling of the osteocyte network, to be the first to truly understand this under-studied area of the metastatic cascade.CONTRA has the potential to revolutionise drug development and treatment of metastatic bone disease by providing a leap forward our ability to study the under-explored role of the osteocyte network in metastatic lesions, leveraging cancer-osteocyte crosstalk to identify new therapeutic targets.