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

Authors
  • Wilkie, Mark D.1, 2
  • Anaam, Emad A.1
  • Lau, Andrew S.1, 2
  • Rubbi, Carlos P.1
  • Jones, Terence M.1, 2
  • Boyd, Mark T.1
  • Vlatković, Nikolina1
  • 1 Department of Molecular & Clinical Cancer Medicine, Cancer Research Centre, University of Liverpool, 200 London Road, Liverpool, L3 9TA, UK
  • 2 Department of Otorhinolaryngology – Head & Neck Surgery, University Hospital Aintree, Lower Lane, Liverpool, L9 7AL, UK
Type
Published Article
Journal
Cancer letters
Publication Date
May 28, 2020
Volume
478
Pages
107–121
Identifiers
DOI: 10.1016/j.canlet.2020.02.032
PMID: 32113989
PMCID: PMC7133053
Source
PubMed Central
Keywords
Disciplines
  • Article
License
Unknown

Abstract

What is already known • TP53 mutations are the most common genetic mutation in many cancers, including head and neck cancers. •Patients with mutated p53 display poor prognosis but no method exists for selectively treating these patients What this study adds •We identify and confirm that p53 status (mutant or normal) determines tumour cell metabolic profile •Metabolic changes induced by loss of p53 function determine sensitivity to metabolic inhibition in combination with the mainstay of current therapy-radiation, and provide an opportunity to increase radiation sensitivity in p53 mutated cells •The results suggest that a strategy for treating patients with mutations in TP53 could be readily developed combining the current standard of care (radiotherapy) with short term inhibition of a metabolic pathway (glycolysis).

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