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KCNH2 (hERG; Kv11.1; human ether-à-go-go-related gene potassium channel)
is a voltage-gated potassium channel that conducts the rapid delayed-rectifier
potassium current, IKr, and is essential for normal cardiac ventricular
repolarization. In several cancers, hERG expression or activity is increased and
can support tumour-cell proliferation, survival, migration, invasion and
angiogenesis. Experimental hERG inhibition has reduced proliferation and induced
cell-cycle arrest or apoptosis in some cancer models, so the typical
cancer-associated direction is up, while the desired anticancer
modulation may be down or channel inhibition. However, systemic
hERG inhibition is a major safety concern because it can delay cardiac
repolarization, prolong the QT interval and increase the risk of torsades de
pointes and other ventricular arrhythmias. Therefore, hERG is
both as a potential cancer target and a high-priority cardiac safety target.
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