Oxidative stress and cancer pain.
Breast cancers are the most common source of metastases to bone, of which cancer-induced bone pain is a frequent pathological feature. Cancer-induced bone pain is a unique pain state with multiple determinants that remains to be well understood and managed. Current standard treatments are limited by dose-dependent side effects that can reduce the quality of life of patients. Glutamate is a neurotransmitter and bone cell-signalling molecule that is released via the system x(c)(-) cystine/glutamate antiporter from cancer cell types that frequently metastasize to bone, including breast cancers. In cancer cells, glutamate release is understood to be a side effect of the cellular response to oxidative stress that upregulates the expression and activity of system x(c)(-) to promote the increased import of cystine. Attenuation of glutamate release from cancer cells has been demonstrated to result in reductions in associated cancer-induced bone pain in animal models. This review examines the clinical implications of attenuating cystine uptake and glutamate release in the treatment of cancer-induced bone pain.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON L8N 3Z5, Canada.
Robert G
RG
Ungard
Eric P
EP
Seidlitz
Gurmit
G
Singh
D001859:Bone Neoplasms / Q000378:metabolism* / Q000556:secondary*; D001842:Bone and Bones / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D003545:Cysteine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D059226:Nociceptive Pain / Q000378:metabolism*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D003545:Cysteine