Penelope Ottewell
University of Sheffield, UK
Title: Inhibition of RANK/RANKL interactions preventovariectomy-induced growth of disseminated breast cancer cells in bone
Biography
Biography: Penelope Ottewell
Abstract
Dormant disseminated tumour cells can be detected in the bone marrow of breast cancer patients several years after resection of the primary tumour. The majority of these patients will remain asymptomatic, however, approximately 15% will go on to develop overt bone metastases and this condition is currently incurable. The reason why these dormant cells are stimulated to proliferate and form bone tumours in some patients and not others remains to be elucidated. We have recently shown that in an in vivo model, increasing bone turnover by ovariectomy stimulated proliferation of disseminated tumour cells, resulting in formation of bone metastasis. This awakening of MDA-MB-231 tumour cells in bone from a dormant to a proliferative state was prevented following administration of the antiresorptive drug zoledronic acid and therefore appeared to be driven by osteoclast mediated mechanisms. In agreement with this hypothesis we have also shown that disruption of RANK-RANKL interactions following administration of OPG-Fc inhibits growth of these dormant tumour cells in vivo. Our pre-clinical data support early intervention with anti-resorptive therapy in a low-oestrogen environment to prevent development of bone metastases.