Anticancer drugs that target metabolism: Is dichloroacetate the new paradigm?

摘要: Recent findings in the fields of oncogenic regulation metabolism, mitochondrial function and macromolecular synthesis have brought tumor metabolism Warburg effect back into scientific limelight. A number metabolic pathways that seem to be important for growth are being touted as novel targets anticancer drug development. One candidates this class drugs investigated is dichloroacetate (DCA), a molecule used over 25 years treatment children with inborn errors function. This pyruvate mimetic compound stimulates by inhibiting family regulatory dehydrogenase kinases (PDK1-4). The stimulation function, at expense glycolysis, reverses thought block advantage highly glycolytic tumors. Interestingly, some recent vitro shown very modest "antitumor cell activity" DCA when cells treated dish. However, several studies reported model apparent paradox raises question, how do we evaluate cancer designed target metabolism? Traditional approaches development assays first pass potential lead compounds. fact has better vivo activity than suggests there unique aspects solid difficult recapitulate may determining effectiveness drugs.