2009
DOI: 10.1111/j.1349-7006.2009.01294.x
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Osteoclast‐targeting small molecules for the treatment of neoplastic bone metastases

Abstract: Osteoclasts are highly specialized cells that resorb bone, and their abnormal activity is implicated in a variety of human bone diseases. In neoplastic bone metastasis, the bone destruction caused by osteoclasts is not only associated with the formation and progression of metastatic lesions, but also could contribute to frequent complications such as severe pain and pathological fractures, which greatly diminish the quality of life of patients. Bisphosphonates, potent antiresorptive drugs, have been shown to h… Show more

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Cited by 38 publications
(42 citation statements)
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“…Systemically administered bisphosphonates were the first (FDA-)approved bonetargeted drug therapy for treatment of bone metastases [34]. Bisphosphonates have a high affinity for hydroxy-apatite crystals in mineralized bone where they accumulate and are internalized by osteoclasts, inducing osteoclast apoptosis, thereby inhibiting bone resorption [23,37,55,56].…”
Section: Bisphosphonatesmentioning
confidence: 99%
“…Systemically administered bisphosphonates were the first (FDA-)approved bonetargeted drug therapy for treatment of bone metastases [34]. Bisphosphonates have a high affinity for hydroxy-apatite crystals in mineralized bone where they accumulate and are internalized by osteoclasts, inducing osteoclast apoptosis, thereby inhibiting bone resorption [23,37,55,56].…”
Section: Bisphosphonatesmentioning
confidence: 99%
“…Bone metastases are predominant in breast (65 − 75%), prostate (65 − 75%), thyroid (60%), lung (30 − 40%), and kidney cancer (20 − 25%) [2]. The patients with bone metastases suffer from high death rate, pain, and decreased quality of life, resulting from osteoclastic and/or osteoblastic bone lesions and its clinically important complications such as fracture, need for radiotherapy and/or chemotherapy, spinal cord compression, or hypercalcemia [3]. Patients who are diagnosed with bone metastases generally cannot be treated curatively in spite of extensive research, e.g., only 46% of patients with prostate cancer, 20% of patients with breast cancer, and less than 10% of patients with lung cancer are still alive five years after the diagnosis of bone metastases [2].…”
Section: Introductionmentioning
confidence: 98%
“…Recently, several targeted therapeutic agents that inhibit osteoclastmediated bone resorption (Vacuolar H + -ATPase inhibitors, RANKL inhibitor, c-Src Inhibitors, αvβ3 integrin inhibitors, Cathepsin K inhibitors, bisphosphonates, etc) [3,7] and restore osteoblast functions (DKK-1 inhibitors, Activin A inhibitors, etc) [8] have been studied or evaluated in clinical trials. Although these do reduce some degree of metastatic growth, providing symptomatic relief and regression of bone disease, none of them have been proven to significantly control tumor progression or improve overall survival [9].…”
Section: Introductionmentioning
confidence: 99%
“…Since the deregulation of osteoclast functions has been associated with several diseases including osteoporosis and bone-metastasis, considerable and widespread attention has been focused on compounds that affect osteoclastogenesis and the functions of osteoclasts for the treatment of osteoclast-related diseases. 4,5 In the present study, we isolated halenaquinone 6 (1) (Fig. 1) from the marine sponge Petrosia alfiani as an inhibitor of osteoclastogenic differentiation of murine RAW264 cells.…”
Section: Introductionmentioning
confidence: 99%