The aim of this study was to generate and characterize antibodies in single chain Fragment variable (scFv) format directed to an emerging cancer biomarker, the <i>human ether-à-go-go-related gene-1</i> (hERG1) potassium channel, and to obtain a proof of concept for their potential use for <i>in vivo</i> molecular imaging.
The function of Kv11.1 is emerging in breast cancer biology, as a growing body of evidence indicates that the hERG1/Kv11.1 potassium channel is aberrantly expressed in several cancer types including breast cancers.The biological effects of Kv11.1 channel blockers and their associated side effects are very well known but the potential use of Kv11.1 activators as an anticancer strategy are still unexplored.
The most important conclusion of this study is that selective hERG1 channel blockers have therapeutic potential in the treatment of hERG1-expressing cancers.
Our data demonstrate that HERG1 expression is a biologically and clinically relevant feature in head and neck squamous cell carcinoma progression and also during malignant transformation, and a promising candidate as cancer risk marker and therapeutic target for head and neck squamous cell carcinoma prevention and treatment.
Previous studies have demonstrated that human ether-à-go-go-related potassium channel (hERG1) is highly expressed in many tumor cell lines, as well as in primary human cancers, and, hence, have a critical role in cell cycle progress and proliferation.
Data here reported, support the hypothesis that hERG1 expression marks an early step of the progression of normality to cancer in the human esophagus through a metaplastic and dysplastic stage.
In addition, we present evidence that, in GBM cell lines, hERG1 channel activity actively contributes to malignancy by promoting vascular endothelial growth factor secretion, thus stimulating the neoangiogenesis typical of high-grade gliomas.