Voltage-gated calcium channel (VGCC) and other tumor-associated ion channels (VGCC)

Voltage-gated calcium channels (VGCCs) are complex multi-subunit proteins that mediate the entry of calcium ions into cells upon membrane depolarization, acting as vital transducers of electrical signals into intracellular biological responses (Source: StatPearls, 'Physiology, Voltage-Gated Calcium Channels'). In various malignancies, VGCCs and other tumor-associated ion channels (such as certain potassium and sodium channels) are aberrantly expressed or regulated, a phenomenon often termed 'onco-channelopathy' (Source: Nature Reviews Cancer, 'Ion channels in cancer: from diagnosis to therapy'). These channels contribute to the hallmarks of cancer by promoting cell proliferation, inhibiting apoptosis, and facilitating epithelial-mesenchymal transition and metastasis through the modulation of calcium-dependent signaling cascades like MAPK/ERK and PI3K/Akt (Source: Frontiers in Pharmacology, 'Voltage-Gated Calcium Channels in Cancer'). While traditionally targeted for cardiovascular and neurological disorders, these channels are increasingly recognized as potential oncology targets due to their role in tumor pathophysiology (Source: PubMed, PMID: 28633251). However, the widespread physiological roles of these channels in the heart and brain necessitate the development of highly selective inhibitors or tumor-targeted delivery systems to minimize dose-limiting systemic toxicities (Source: Journal of Clinical Investigation, 'Ion channels as targets for cancer therapy').

Other names

VGCCsVoltage-dependent calcium channelsOnco-channelsTumor-associated ion channelsCalcium channel subunits

Inhibition of calcium ion influx through the channel pore or modulation of channel gating properties to disrupt downstream signaling pathways involved in cell survival and proliferation (Source: PubMed, PMID: 30135518).