International Journal Of Bilogical Sciences
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Targeting Tumor Metabolism for Cancer Treatment: Is Pyruvate Dehydrogenase Kinases (PDKs) a Viable Anticancer Target?
Wen Zhang, Shao-Lin Zhang, Xiaohui Hu, Kin Yip Tam
Drug Development Core, Faculty of Health Sciences, University of Macau, Macau, China Corresponding author: Tam, K.Y. (email@example.com). Tel.: +853-88224988; fax: +853-88222314
Cancer remains a lethal threat to global lives. Development of novel anticancer therapeutics is still a challenge to scientists in the field of biomedicine. In cancer cells, the metabolic features are significantly different from those of normal ones, which are hallmarks of several malignancies. Recent studies brought atypical cellular metabolism, such as aerobic glycolysis or the Warburg effect, into the scientific limelight. Targeting these altered metabolic pathways in cancer cells presents a promising therapeutic strategy. Pyruvate dehydrogenase kinases (PDKs), key enzymes in the pathway of glucose metabolism, could inactivate the pyruvate dehydrogenase complex (PDC) by phosphorylating it and preserving the substrates pyruvate, lactate and alanine for gluconeogenesis. Overexpression of PDKs could block the oxidative decarboxylation of pyruvate to satisfy high oxygen demand in cancer cells, while inhibition of PDKs could upregulate the activity of PDC and rectify the balance between the demand and supply of oxygen, which could lead to cancer cell death. Thus, inhibitors targeting PDKs represent a promising strategy for cancer treatment by acting on glycolytic tumors while showing minimal side effects on the oxidative healthy organs. This review considers the role of PDKs as regulator of PDC that catalyzes the oxidative decarboxylation of pyruvate in mitochondrion. It is concluded that PDKs are solid therapeutic targets. Inhibition of PDKs could be an attractive therapeutic approach for the development of anti-cancer drugs
aerobic glycolysis; pyruvate dehydrogenase complex; pyruvate dehydrogenase kinases; tumor metabolism.
Date Deposited : 08 Mar 2016 13:43
Official URL: http://www.ijbs.com/v11i12
Last Modified : 08 Mar 2016 13:43
Volume 11, Number 12, - 2015 , ISSN 1449-2288
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