Bone is one of the most common sites for metastatic disease. Virtually incurable, bone cancers are destructive and have a high risk of disease recurrence. Anti-resorptive agents, such as bisphosphonates and Denosumab, are mainstay treatment for bone metastatic disease, reducing further bone loss and fracture. Remarkably, anti-resorptive agents have been shown to improve disease free survival and reduce disease recurrence, suggesting that anti-resorptives could also modify early disease stages.
Our work is focused on determining the cellular mechanisms within the bone micro-environment behind this clinical finding, thereby improving the application of these agents in the clinical management of bone metastatic disease. The bone microenvironment provides a fertile soil which supports tumour cell engraftment and survival. We pioneered a novel intravital imaging technique in bone which revealed for the first time that long lived chemo-resistant dormant tumour cells reside in a niche in bone and can be reactivated through osteoclastic bone resorption to drive disease recurrence. Further, this imaging technique allowed us to define novel osteoclast biology, a finding which is likely to have implications in control of tumour cell reactivation. Through visualising tumour cell and osteoclast interactions in real time in vivo we are revealing new insight into how modifying this interaction, with anti-resorptive agents, may supress tumour cell reactivation and prevent metastatic outgrowth. The outcomes of this work may prevent the outgrowth of cancers in bone, thereby impacting significantly on cancer survivorship and quality of life.