Dichloroacetate Effective Against Aggressive Brain Cancer

Orphan drug dichloroacetate (DCA) has been found effective against aggressive brain cancer in a small Canadian study. Orphan drugs are meant to treat rare medical conditions. DCA is now used to treat a rare enzyme disorder in children, but researchers have found it useful in brain tumor too.

The study published in Wednesday's online issue of the journal Science Translational Medicine showed tumours responded to DCA by changing their metabolism. Because DCA has a unique way of killing cancer cells, the new findings represent progress in a new area of cancer research that may stunt growth of tumours without harming healthy cells.

“Solid tumors, including the aggressive primary brain cancer glioblastoma multiforme, develop resistance to cell death, in part as a result of a switch from mitochondrial oxidative phosphorylation to cytoplasmic glycolysis. This metabolic remodeling is accompanied by mitochondrial hyperpolarization. We tested whether the small-molecule and orphan drug dichloroacetate (DCA) can reverse this cancer-specific metabolic and mitochondrial remodeling in glioblastoma,” wrote Evangelos D. Michelakis of the University of Alberta and his colleagues.

Freshly isolated glioblastomas from 49 patients showed mitochondrial hyperpolarization, which was rapidly reversed by DCA. In a separate experiment with five patients who had glioblastoma, they prospectively secured baseline and serial tumor tissue, developed patient-specific cell lines of glioblastoma and putative glioblastoma stem cells, and treated each patient with oral DCA for up to 15 months. There too the researchers tasted success.