hERG1 Potassium Channels: Novel Biomarkers in Human Solid Cancers

Abstract

Because of their high incidence and mortality solid cancers are a major health problem worldwide. Although several new biomarkers and potential targets for therapy have been identified through biomolecular research in the last years, the effects on patients' outcome are still unsatisfactory. Increasing evidence indicates that hERG1 potassium channels are overexpressed in human primary cancers of different origin and several associations between hERG1 expression and clinicopathological features and/or outcome are emerging. Aberrant hERG1 expression may be exploited either for early diagnosis (especially in those cancers where it is expressed in the initial steps of tumor progression) or for therapy purposes. Indeed, hERG1 blockage impairs tumor cell growth both in vitro and in vivo in preclinical mouse model. hERG1-based tumor therapy in humans, however, encounters the major hindrance of the potential cardiotoxicity that many hERG1 blockers exert. In this review we focus on recent advances in translational research in some of the most frequent human solid cancers (breast, endometrium, ovary, pancreas, esophagus, stomach, and colorectum) that have been shown to express hERG1 and that are a major health problem.

Figure 1

Structure of hERG1 potassium channel. PAS: PAS (acronym of Per Arnt Sim) domain; cNBD (cyclic nucleotide binding domain).

Figure 2

Incidence and mortality for the human solid tumors discussed in the present review. Colorectal, lung, esophageal, pancreatic, and gastric cancers in both sexes (a) and breast, corpus uteri, and ovarian cancers in females (b). Source: GLOBOCAN 2012.