Targeting the receptor activator of nuclear factor-kappaB (RANK) ligand in prostate cancer bone metastases.
Newly formed bone in the typically osteoblastic bone metastases from prostate cancer shows characteristics of woven bone, e.g. marked defects in mineralization and microstructure. Adding to the reduced mechanical strength of prostate cancer bone metastasis is an increasingly recognized osteolytic component. The existence of osteoclasts in osteoblastic bone metastases and concomitant increases in urine or serum markers for bone resorption are reported in affected patients. Pathologically increased osteoclastic bone resorption is a key mediator of the clinical complications from bone metastases, among them fractures, spinal cord compression and bone pain. The receptor activator of nuclear factor (NF)-kappaB ligand (RANKL) pathway has been identified as the main driving force for osteoclastogenesis and resulting bone resorption. Emerging data indicate that bone marrow-derived RANKL might also constitute a chemoattractant factor for RANK-expressing tumour cells that is likely to contribute to the pathogenesis of bone metastases, including those arising from prostate cancer. Cumulative evidence supports RANKL inhibition as a therapeutic goal for the treatment and prevention of bone metastases from prostate cancer.
Saad
Fred
F
University of Montreal, Montreal, Quebec, Canada. fred.saad@umontreal.ca
Markus
Richard
R
Goessl
Carsten
C
D001859:Bone Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary*; D001862:Bone Resorption / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008297:Male; D010010:Osteoclasts / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000473:pathology*; D053245:RANK Ligand / Q000037:antagonists & inhibitors* / Q000378:metabolism; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism
D053245:RANK Ligand; D053246:Receptor Activator of Nuclear Factor-kappa B