Pilot: Understanding the Role of Sulfiredoxin in Glucose Metabolism in Non-Small Cell Lung Cancer

Grants and Contracts Details

Description

Abstract Sulfiredoxin (SRX) is an oxidoreductase that restores the peroxidase activity of peroxiredoxin (PRX) to maintain cellular redox balance, and is a critical activator of redox-related signaling that promotes cell survival.The goal of this pilot study is to further validate the role of SRX in regulating glucose metabolism and to determine an effective strategy of targeting SRX for NSCLC treatment. We hypothesize that SRX functions as a metabolic switch in NSCLC cells to reprogram the route of glucose metabolism by regulating the expression and/or activities of involving enzymes, and targeted inhibition of SRX together with counteractive blocking of the PPP may provide synergistic effect of eliminating NSCLC. We will test this hypothesis through the completion of two specific aims: (1) To elucidate potentially parallel mechanisms by which loss of SRX in NSCLC cells reprograms glucose metabolism through the inhibition of glycolysis and collateral activation of the PPP. (2) To demonstrate the efficacy of killing NSCLC cells through the inhibition of SRX and concurrent blocking of the PPP. At the end of the funding period, all results and concepts will be consolidated as the foundation for an NCI ROl grant entitled "Treatment of NSCLC through the Inhibition of SRX and Concurrent Blocking of the PPP". Aims of this R0l will include further study of the unique role of the SRX-HDAC4/6-6PGD axis in the activation of the PPP in NSCLC, and the investigation of the efficacy of the strategy of killing NSCLC cells using 1SO-1 combined with the PPP blocker, along with the study of toxicity, maximal tolerance dose, pharmacokinetics and preclinical testing in appropriate mouse models.
StatusActive
Effective start/end date3/1/1712/31/26

Funding

  • National Institute of General Medical Sciences

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