Sodium dichloroacetate (DCA) is an investigational medicinal product which has a potential anticancer preparation as a metabolic regulator in
cancer cells' mitochondria. Inhibition of
pyruvate dehydrogenase kinases by DCA keeps the
pyruvate dehydrogenase complex in the active form, resulting in decreased
lactic acid in the tumor microenvironment. This literature review displays the preclinical research data on DCA's effects on the cell
pyruvate dehydrogenase deficiency,
pyruvate mitochondrial oxidative phosphorylation,
reactive oxygen species generation, and the Na+-K+-2Cl- cotransporter expression regulation in relation to gender. It presents DCA pharmacokinetics and the hepatocarcinogenic effect, and the safety data covers the DCA monotherapy efficacy for various human
cancer xenografts in vivo in male and female animals. Preclinical
cancer researchers report the synergistic effects of DCA combined with different drugs on
cancer by reversing resistance to
chemotherapy and promoting cell apoptosis. Researchers note that female and male animals differ in the mechanisms of cancerogenesis but often ignore studying DCA's effects in relation to gender. Preclinical gender-related differences in DCA pharmacology, pharmacological mechanisms, and the elucidation of treatment efficacy in gonad
hormone dependency could be relevant for individualized
therapy approaches so that gender-related differences in treatment response and safety can be proposed.