Bone metastases: molecular mechanisms and novel therapeutic interventions.
It has been long recognized that skeleton represents one of the most favored metastatic sites for common cancers like breast and prostate. During the last decade the molecular mechanisms that are responsible for the development of bone metastasis have been gradually illuminated. It appears that the bone microenvironment has a pivotal role in this process. Metastatic tumor cells interact with bone triggering a cascade of molecular events that produce osteolytic and/or osteoblastic phenomena. In this review, we summarize and discuss the most significant factors and signaling pathways implicated in bone colonization. Moreover, based on the recent literature and data, we foresee the need for designing novel agents that will efficiently disrupt these interactions among cancer cells and bone microenvironment, bringing hope for more effective treatments.
Papachristou
Dionysios J
DJ
Department of Anatomy-Histology-Embryology, University of Patras School of Medicine, 26500, Patras, Greece.
Basdra
Efthimia K
EK
Papavassiliou
Athanasios G
AG
D000818:Animals; D001713:Biphenyl Compounds / Q000627:therapeutic use; D001859:Bone Neoplasms / Q000188:drug therapy / Q000556:secondary*; D016723:Bone Remodeling / Q000502:physiology; D001943:Breast Neoplasms / Q000473:pathology; D056657:Cathepsin K / Q000037:antagonists & inhibitors; D054377:Chemokine CXCL12 / Q000502:physiology; D004164:Diphosphonates / Q000627:therapeutic use; D019332:Endothelin-1 / Q000502:physiology; D005260:Female; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology; D008297:Male; D014411:Neoplastic Stem Cells / Q000187:drug effects; D010006:Osteoblasts / Q000502:physiology; D010010:Osteoclasts / Q000473:pathology / Q000502:physiology; D010014:Osteolysis / Q000503:physiopathology; D044162:Parathyroid Hormone-Related Protein / Q000502:physiology; D011471:Prostatic Neoplasms / Q000473:pathology; D053245:RANK Ligand / Q000502:physiology; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000502:physiology; D019718:Receptors, CXCR4 / Q000502:physiology; D015398:Signal Transduction; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology; D051176:beta Catenin / Q000502:physiology
D001713:Biphenyl Compounds; C515255:CXCL12 protein, human; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D004164:Diphosphonates; D019332:Endothelin-1; D044162:Parathyroid Hormone-Related Protein; D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B; D019718:Receptors, CXCR4; C505686:TNFRSF11A protein, human; D051153:Wnt Proteins; D051176:beta Catenin; D014568:Urokinase-Type Plasminogen Activator; D056657:Cathepsin K; C527128:odanacatib