title: Future directions of bone-targeted therapy for metastatic breast cancer.
abstract: Bone is the most common metastatic site for breast cancer, and bone metastases can cause pain as well as risk of pathological fractures. Emerging treatments for metastatic bone disease have arisen from advances in our understanding of the unique cellular and molecular mechanisms that contribute to bone metastasis. The interaction between tumor cells and the bone microenvironment results in a 'vicious cycle' that increases both bone destruction and tumor burden. The tumor secretes factors, such as parathyroid hormone-related peptide, that stimulate osteoclastogenesis. Similarly, the bone stroma produces growth factors, such as transforming growth factor β, that promote tumor growth in bone. Therapeutic targeting of these microenvironmental factors is under intensive investigation. Other attractive therapeutic targets include signaling molecules, such as receptor activator of nuclear factor κB ligand, Src kinase, and cathepsin K, all of which regulate osteoclast function, and chemokine receptor 4, which is involved in the homing of tumor cells to bone. In this Review, we describe the progress and future directions of novel bone-targeted therapies that may reduce or prevent destructive bone metastasis from breast cancer. Novel modalities for predicting and monitoring treatment response will also be described.
authors.affiliation: Christus Hospital-St Elizabeth, 2830 Calder Street, Beaumont, TX 77702, USA.
authors.forename: Tomifumi
authors.initials: T
authors.lastname: Onishi
authors.forename: Naoki
authors.initials: N
authors.lastname: Hayashi
authors.forename: Richard L
authors.initials: RL
authors.lastname: Theriault
authors.forename: Gabriel N
authors.initials: GN
authors.lastname: Hortobagyi
authors.forename: Naoto T
authors.initials: NT
authors.lastname: Ueno
mesh_terms: D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology*; D056657:Cathepsin K; D002628:Chemoreceptor Cells; D000069448:Denosumab; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000627:therapeutic use; D008024:Ligands; D016328:NF-kappa B; D010281:Parathyroid Hormone; D053245:RANK Ligand / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta; D000077211:Zoledronic Acid; D019061:src-Family Kinases
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D008024:Ligands; D016328:NF-kappa B; D010281:Parathyroid Hormone; D053245:RANK Ligand; D016212:Transforming Growth Factor beta; D000069448:Denosumab; D000077211:Zoledronic Acid; D019061:src-Family Kinases; D056657:Cathepsin K
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