Please use this identifier to cite or link to this item:
|Title:||Targeting STAT3 and oxidative phosphorylation in oncogene-addicted tumors||Authors:||Lee M.
|Keywords:||Cancer cell metabolism
Oxidative phosphorylation (OXPHOS)
STAT3 signaling pathways
|Issue Date:||2019||Publisher:||Elsevier B.V.||Citation:||Lee M., Hirpara J.L., Eu J.-Q., Sethi G., Wang L., Goh B.-C., Wong A.L. (2019). Targeting STAT3 and oxidative phosphorylation in oncogene-addicted tumors. Redox Biology 25. ScholarBank@NUS Repository. https://doi.org/10.1016/j.redox.2018.101073||Abstract:||Drug resistance invariably limits the response of oncogene-addicted cancer cells to targeted therapy. The upregulation of signal transducer and activator of transcription 3 (STAT3) has been implicated as a mechanism of drug resistance in a range of oncogene-addicted cancers. However, the development of inhibitors against STAT3 has been fraught with challenges such as poor delivery or lack of specificity. Clinical experience with small molecule STAT3 inhibitors has seen efficacy signals, but this success has been tempered by drug limiting toxicities from off-target adverse events. It has emerged in recent years that, contrary to the Warburg theory, certain tumor types undergo metabolic reprogramming towards oxidative phosphorylation (OXPHOS) to satisfy their energy production. In particular, certain drug-resistant oncogene-addicted tumors have been found to rely on OXPHOS as a mechanism of survival. Multiple cellular signaling pathways converge on STAT3, hence the localization of STAT3 to the mitochondria may provide the link between oncogene-induced signaling pathways and cancer cell metabolism. In this article, we review the role of STAT3 and OXPHOS as targets of novel therapeutic strategies aimed at restoring drug sensitivity in treatment-resistant oncogene-addicted tumor types. Apart from drugs which have been re-purposed as OXPHOS inhibitors for-anti-cancer therapy (e.g., metformin and phenformin), several novel compounds in the drug-development pipeline have demonstrated promising pre-clinical and clinical activity. However, the clinical development of OXPHOS inhibitors remains in its infancy. The further identification of compounds with acceptable toxicity profiles, alongside the discovery of robust companion biomarkers of OXPHOS inhibition, would represent tangible early steps in transforming the therapeutic landscape of cancer cell metabolism. © 2018 The Authors||Source Title:||Redox Biology||URI:||https://scholarbank.nus.edu.sg/handle/10635/175941||ISSN:||22132317||DOI:||10.1016/j.redox.2018.101073|
|Appears in Collections:||Elements|
Show full item record
Files in This Item:
|targeting OXPHOS in oncogene-addicted tumours.pdf||1.22 MB||Adobe PDF|
checked on Apr 7, 2021
checked on Apr 9, 2021
checked on Apr 9, 2021
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.