The Kv10.1 Channel: A Promising Target in Cancer

Abstract

Carcinogenesis is a multistage process involving the dysregulation of multiple genes, proteins, and pathways that make any normal cell acquire a cancer cell phenotype. Therefore, it is no surprise that numerous ion channels could be involved in this process. Since their discovery and subsequent cloning, ion channels have been established as therapeutic targets in excitable cell pathologies (e.g., cardiac arrhythmias or epilepsy); however, their involvement in non-excitable cell pathologies is relatively recent. Among all ion channels, the voltage-gated potassium channels Kv10.1 have been established as a promising target in cancer treatment due to their high expression in tumoral tissues compared to low levels in healthy tissues.

A Multidisciplinary Approach Establishes a Link between Transglutaminase 2 and the Kv10.1 Voltage-Dependent K+ Channel in Breast Cancer

“…Considering potential therapeutic strategies, it could be interesting to combine the use of AA9 with inhibitors of the Kv10.1 channel, known to regulate cell cycle [61], drug resistance and tumor progression [91], some of which have already been proposed for clinical applications [78]. In particular, it will be interesting to analyze the effectiveness of the potential synergistic action of TG2 inhibitors and astemizole which are known to work in combination with other drugs [92,93] which in this case would also have the same target, the Kv10.1 channel [94].…”

Fluorescent membrane potential assay for drug screening on Kv10.1 channel: identification of BL-1249 as a channel activator

“…Kv10.1 belong to the superfamily of voltage-gated potassium channels and is assembled as homotetramers ( Whicher and MacKinnon, 2016 ). Diverse authors have shown an overexpression of Kv10.1 in cancer samples, contrasting with a low expression in healthy tissues ( Farias et al, 2004 ; Hemmerlein et al, 2006 ; Ortiz et al, 2011 ; Martínez et al, 2015 ; Luis et al, 2022a ). Also, it has been described that Kv10.1 overexpression is associated with increased cell proliferation, angiogenesis, and chemo- and radio-resistance phenotype ( Pardo et al, 1999 ; Downie et al, 2008 ; Bai et al, 2013 ; Luis et al, 2022b ).…”