Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer.

Abstract

Metastasis to the bone is most frequently observed in advanced cases of breast and prostate cancer. The latent development of overt metastatic lesions is associated with debilitating skeletal morbidity and eventual patient mortality. Secondary tumours in bone are derived from disseminated tumour cells (DTCs) that enter into a state of cellular dormancy. The dormant state confers resistance to conventional chemotherapeutic agents and prevents elimination of DTCs from the bone using current drug therapies. Expansion of our presently limited understanding of the molecular mechanisms underpinning disseminated breast and prostate tumour cell dormancy is critical to the future development of novel drug therapies aimed at the removal of DTCs, and thereby, the prevention of bone metastasis. This review provides an overview of the main putative molecular mechanisms underlying cellular dormancy in breast and prostate cancer bone metastasis reported from multiple experimental in vitro and in vivo models.