Rapamycin inhibits osteolysis and improves survival in a model of experimental bone metastases.
Breast cancer metastasis to bone results in pain, pathological fractures and hypercalcemia. Activation of osteoclasts is critical for the formation of osteolytic lesions by metastasizing tumors. Although the potent drugs, zoledronic acid and Denosumab were introduced, the presence of resistant or intolerant cases necessitated the continued search of osteoclast-targeting treatments. Rapamycin acts through the mTOR pathway, which is important for osteoclast formation. Mouse mammary carcinoma 4T1 cells were injected into the tibia of balb/c mice. Rapamycin treatment significantly decreased the osteoclast population and osteolysis associated with experimental metastases. Our data indicate the benefit of rapamycin in treating metastases-associated osteolytic disease.
Faculty of Dentistry, McGill University, Montreal, Quebec, Canada H3A 1A4.
Osama
O
Hussein
Kerstin
K
Tiedemann
Monzur
M
Murshed
Svetlana V
SV
Komarova
D000818:Animals; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D002478:Cells, Cultured; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D010006:Osteoblasts / Q000187:drug effects / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects; D010014:Osteolysis / Q000517:prevention & control*; D020123:Sirolimus / Q000494:pharmacology / Q000627:therapeutic use*
D020123:Sirolimus