Bioelectric pharmacology of cancer: A systematic review of ion channel drugs affecting the cancer phenotype

Abstract

Cancer is a pernicious and pressing medical problem; moreover, it is a failure of multicellular morphogenesis that sheds much light on evolutionary developmental biology. Numerous classes of pharmacological agents have been considered as cancer therapeutics and evaluated as potential carcinogenic agents; however, these are spread throughout the primary literature. Here, we briefly review recent work on ion channel drugs as promising anti-cancer treatments and present a systematic review of the known cancer-relevant effects of 109 drugs targeting ion channels. The roles of ion channels in cancer are consistent with the importance of bioelectrical parameters in cell regulation and with the functions of bioelectric signaling in morphogenetic signals that act as cancer suppressors. We find that compounds that are well-known for having targets in the nervous system, such as voltage-gated ion channels, ligand-gated ion channels, proton pumps, and gap junctions are especially relevant to cancer. Our review suggests further opportunities for the repurposing of numerous promising candidates in the field of cancer electroceuticals.