Douglas Krafte, Ph.D.
A study in last month’s Nature Neuroscience supports emerging and exciting potential new use for ion channel blocking drugs. Most known for their neurological activity, ion channel blockers may have a role in treating cancer.
Perpetual challenges in cancer treatment include therapy side effects, relapse and acquired treatment resistance. These factors are fueling a need for novel molecular targets to develop new therapeutic options.
More than 20 percent of approved drugs for human diseases target ion channels, but none have been approved to date for cancer treatment. Given their location on the cell membrane and well known pharmacology, ion channel proteins are highly ‘druggable’ targets.
Recent evidence has suggested a role for ion channels in driving malignancy (for a review, see http://rstb.royalsocietypublishing.org/content/369/1638/20130108).
In the paper entitled “EAG2 potassium channel with evolutionarily conserved function as a brain tumor target,” researchers at the University of California San Francisco collaborating with Toronto’s Hospital for Sick Children showed that the potassium channel blocking drug thioridazine slowed the growth of a type of brain cancer in fruit flies and mice, and was subsequently used to slow the growth of the same type of cancer in a human patient.
Although the UCSF study demonstrated the shrinkage of an EAG2-expressing metastatic tumor, the patient was unable to tolerate thioridazine’s side effects and ultimately succumbed to disease. The authors state that their discovery encourages the future development of second-generation drugs with greater specificity for blocking EAG2 channels as well as substantial CNS access and better toxicity profiles. Previous studies of other types of cancer cells suggest that similar ion channels, including the EAG1 potassium channel, might also be promising targets for new cancer therapies bolstering ion channel modulators as a potential new avenue for cancer treatment.