The Role of Pyruvate Dehydrogenase Kinase-4 (PDK4) in Bladder Cancer and Chemoresistance.

ABSTRACT: Advanced bladder cancer remains a major source of mortality, with poor treatment options. Cisplatin-based chemotherapy is the standard treatment, however many patients are or become resistant. One potential cause of chemoresistance is the Warburg effect, a metabolic switch to aerobic glycolysis that occurs in many cancers. Upregulation of the pyruvate dehydrogenase kinase family (PDK1-PDK4) is associated with aerobic glycolysis and chemoresistance through inhibition of the pyruvate dehydrogenase complex (PDH). We have previously observed upregulation of PDK4 in high-grade compared with low-grade bladder cancers. We initiated this study to determine if inhibition of PDK4 could reduce tumor growth rates or sensitize bladder cancer cells to cisplatin. Upregulation of PDK4 in malignant bladder

SUBMITTER: Woolbright BL 

PROVIDER: S-EPMC6724734 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature