Emerging therapeutic targets in breast cancer bone metastasis.
In the past decade, our understanding of the molecular mechanisms that underlie breast cancer pathology and progression has dramatically improved. Using this knowledge, we have identified additional targets and developed novel therapeutic interventions in breast cancer. Together, these translational research efforts are helping to usher us into an age of personalized cancer therapy. Metastasis to bone is a common and devastating consequence of breast cancer. Bisphosphonates, which represent the current gold standard in bone metastasis therapies, are being improved with newer and more efficacious generations of these compounds being developed. Breast cancer growth in the bone requires activation of various signaling pathways in both cancer cells and stromal cells, including those that are stimulated by TGF-beta and RANKL, and mediated through the Src tyrosine kinase. Bone cells and cancer cells alike express promising targets for therapeutic intervention, including Cathepsin K, CXCR4 and GPNMB. In this article we discuss the molecular mechanisms behind these pro-metastatic molecules and review the most recent findings in the clinical development of their associated targeted therapies.
Rose
April A N
AA
Department of Medicine, Goodman Cancer Centre, McGill University, QC H3A 1A3, Canada.
Siegel
Peter M
PM
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D001943:Breast Neoplasms / Q000473:pathology*; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006801:Humans
D000970:Antineoplastic Agents