The Importance of Gender-Related Anticancer Research on Mitochondrial Regulator Sodium Dichloroacetate in Preclinical Studies In Vivo
Stakišaitis D (1,2), Juknevičienė M (3), Damanskienė E (3), Valančiūtė A (3), Balnytė I (3), Alonso MM (4).
(1) Laboratory of Molecular Oncology, National Cancer Institute, 08660 Vilnius, Lithuania.
(2) Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
(3) Department of Histology and Embryology, Medical Academy, Lithuanian University of Health Sciences, 44307 Kaunas, Lithuania.
(4) Department of Pediatrics, Clínica Universidad de Navarra, University of Navarra, 55 Pamplona, Spain.
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.
CITATION Cancers (Basel). 2019 Aug 20;11(8). pii: E1210. doi: 10.3390/cancers11081210