TP53 mutations in head and neck cancer cells determine the Warburg phenotypic switch creating metabolic vulnerabilities and therapeutic opportunities for stratified therapies

• DOI: 10.1016/j.canlet.2020.02.032
• Publication Date: 2020-02-28T08:00:55Z
• Authors: Mark D. Wilkie; Emad A. Anaam; Andrew S. Lau; Carlos P. Rubbi; Terence M. Jones; Mark T. Boyd; Nikolina Vlatković
• Keywords: Warburg Effect; Loss function

Patients with mutated TP53 have been identified as having comparatively poor outcomes compared to those retaining wild-type p53 in many cancers, including squamous cell carcinomas of the head and neck (SCCHN). We examined role regulation metabolism SCCHN cells find that loss function determines Warburg effect these cells. Moreover, this metabolic adaptation creates an Achilles' heel for tumour can be exploited potential therapeutic benefit. Specifically, lacking normal function, whether through mutation or RNAi-mediated downregulation, display a lack flexibility, becoming more dependent on glycolysis losing ability increase energy production from oxidative phosphorylation. Thus, compromised sensitised ionizing radiation by pre-treatment glycolytic inhibitor. These results demonstrate deterministic regulating provide proof principle evidence opportunity patient stratification based status therapeutically using current standard care treatment ionising radiation.