Targeting Tumor Metabolism for Cancer Treatment: Is Pyruvate Dehydrogenase Kinases (PDKs) a Viable Anticancer Target?

摘要: Cancer remains a lethal threat to global lives. Development of novel anticancer therapeutics is still challenge scientists in the field biomedicine. In cancer cells, metabolic features are significantly different from those normal ones, which hallmarks several malignancies. Recent studies brought atypical cellular metabolism, such as aerobic glycolysis or Warburg effect, into scientific limelight. Targeting these altered pathways cells presents promising therapeutic strategy. Pyruvate dehydrogenase kinases (PDKs), key enzymes pathway glucose could inactivate pyruvate complex (PDC) by phosphorylating it and preserving substrates pyruvate, lactate alanine for gluconeogenesis. Overexpression PDKs block oxidative decarboxylation satisfy high oxygen demand while inhibition upregulate activity PDC rectify balance between supply oxygen, lead cell death. Thus, inhibitors targeting represent strategy treatment acting on glycolytic tumors showing minimal side effects healthy organs. This review considers role regulator that catalyzes mitochondrion. It concluded solid targets. Inhibition be an attractive approach development anti-cancer drugs.