Current opinion in supportive and palliative care · 2008
Cathepsin K inhibitors as treatment of bone metastasis.
СтатьяПоддержка исследования: вне правительства СШАОбзорНазвание и аннотация: Перевод в очереди
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Le Gall Céline, Bonnelye Edith, Clézardin Philippe
Аннотация
PURPOSE OF REVIEW: Cancer cells that metastasize to the skeleton are, on their own, rarely able to destroy bone. Instead, they stimulate the function of bone-degrading cells, the osteoclasts, leading to the formation of osteolytic lesions. The purpose of this review is to consider cathepsin K, a cysteine protease produced by osteoclasts, as a therapeutic target for the treatment of patients with osteolytic bone metastases.
RECENT FINDINGS: Cathepsin K plays a key role in osteoclast-mediated bone degradation. It is also produced by cancer cells that metastasize to bone where it functions in proteolytic pathways that promote cancer cell invasion. Highly selective and potent cathepsin K inhibitors have been recently developed and shown to be useful antiresorptive agents to treat osteoporosis. Moreover, preclinical studies show that cathepsin K inhibitors reduce breast cancer-induced osteolysis and skeletal tumor burden. This reduction of skeletal tumor burden is due to the antiresorptive activity of cathepsin K inhibitors, which in turn, deprive cancer cells of bone-derived growth factors that are required for tumor growth.
SUMMARY: Cathepsin K inhibitors are appropriate drugs to treat diseases associated with increased bone loss. However, their chronic use in treating osteoporosis may result in adverse effects because basic nitrogen-containing cathepsin K inhibitors accumulate within acidic organelles such as lysosomes, thereby inhibiting the activity of other cathepsins. These adverse effects should not, however, preclude the use of these drugs in life-threatening diseases such as bone metastasis.
RECENT FINDINGS: Cathepsin K plays a key role in osteoclast-mediated bone degradation. It is also produced by cancer cells that metastasize to bone where it functions in proteolytic pathways that promote cancer cell invasion. Highly selective and potent cathepsin K inhibitors have been recently developed and shown to be useful antiresorptive agents to treat osteoporosis. Moreover, preclinical studies show that cathepsin K inhibitors reduce breast cancer-induced osteolysis and skeletal tumor burden. This reduction of skeletal tumor burden is due to the antiresorptive activity of cathepsin K inhibitors, which in turn, deprive cancer cells of bone-derived growth factors that are required for tumor growth.
SUMMARY: Cathepsin K inhibitors are appropriate drugs to treat diseases associated with increased bone loss. However, their chronic use in treating osteoporosis may result in adverse effects because basic nitrogen-containing cathepsin K inhibitors accumulate within acidic organelles such as lysosomes, thereby inhibiting the activity of other cathepsins. These adverse effects should not, however, preclude the use of these drugs in life-threatening diseases such as bone metastasis.