title: Therapeutic Value of Voltage-Gated Sodium Channel Inhibitors in Breast, Colorectal, and Prostate Cancer: A Systematic Review.
abstract: Although survival rates of breast, colon, and prostate cancers are improving, deaths from these tumors frequently occur due to metastasis. Voltage-gated Na(+) channels (VGSCs) are membrane proteins, which regulate membrane current and cellular migration during nervous system organogenesis. VGSCs are also expressed in fibroblasts, immune cells, glia, and metastatic cancer cells. VGSCs regulate migration and invasion of breast, bowel, and prostate cancer cells, suggesting that they may be novel anti-metastatic targets. We conducted a systematic review of clinical and preclinical studies testing the effects of VGSC-inhibiting drugs in cancer. Two-hundred and four publications were identified, of which two human, two mouse, and 20 in vitro publications were included. In the clinical studies, the effect of these drugs on survival and metastatic relapse is not clear. The 22 preclinical studies collectively suggest that several VGSC-inhibiting drugs inhibit cancer proliferation, migration, and invasion. None of the human and only six of the preclinical studies directly investigated the effect of the drugs on VGSC activity. Studies were difficult to compare due to lack of standardized methodology and outcome measures. We conclude that the benefits of VGSC inhibitors require further investigation. Standardization of future studies and outcome measures should enable meaningful study comparisons.
authors.affiliation: Department of Biology, University of YorkYork, UK; Hull York Medical School, University of YorkYork, UK.
authors.forename: Fabiola
authors.initials: F
authors.lastname: Martin
authors.affiliation: Hull York Medical School, University of York York, UK.
authors.forename: Chiedu
authors.initials: C
authors.lastname: Ufodiama
authors.affiliation: Department of Health Sciences, University of York York, UK.
authors.forename: Ian
authors.initials: I
authors.lastname: Watt
authors.affiliation: Department of Health Sciences, University of York York, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Bland
authors.affiliation: Department of Biology, University of York York, UK.
authors.forename: William J
authors.initials: WJ
authors.lastname: Brackenbury
keywords: anticonvulsants; breast neoplasms; colonic neoplasms; prostatic neoplasms; sodium channels
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