Voltage-gated sodium channels in cancer and their specific inhibitors

Voltage-gated sodium channels (VGSCs) participate in generating and spreading action potentials in electrically excited cells such as neurons and muscle fibers. Abnormal expression of VGSCs has been observed in various types of tumors, while they are either not expressed or expressed at a low level in the matching normal tissue. Hence, this abnormal expression suggests that VGSCs confer some advantage or viability on tumor cells, making them a valuable indicator for identifying tumor cells. In addition, overexpression of VGSCs increased the ability of cancer cells to metastasize and invade, as well as correlated with the metastatic behavior of different cancers. Therefore, blocking VGSCs presents a new strategy for the treatment of cancers. A portion of this review summarizes the structure and function of VGSCs and also describes the correlation between VGSCs and cancers. Most importantly, we provide an overview of current research on various subtype-selective VGSC inhibitors and updates on ongoing clinical studies.