Investigating metabolic heterogeneity in brain tumours

  • Research type

    Research Study

  • Full title

    Identification of metabolic heterogeneity in human brain tumours using 13C labelled glucose and mass spectrometric imaging.

  • IRAS ID

    245107

  • Contact name

    Richard Mair

  • Contact email

    Richard.Mair@cruk.cam.ac.uk

  • Sponsor organisation

    Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge

  • Duration of Study in the UK

    2 years, 0 months, 1 days

  • Research summary

    Heterogeneity within cancer is a source of treatment failure and tumour recurrence. It results from a complex interplay between the tumour genome and the microenvironment within which the tumour resides. The relationship between tumour heterogeneity and metabolism is unknown. Several recent studies have investigated how tumours employ multiple carbon sources (glucose, lactate, acetate, glutamine) to generate macromolecules as well as ATP for proliferation and cellular survival. Resolution within these investigations has been limited and the underlying pattern of heterogeneity is often lost. We plan to use state of the art 2-dimensional mass spectrometry to investigate the pattern of metabolism within 13-C enriched brain tumour specimens. This will be coupled with genomic, epigenomic and proteomic techniques to investigate causal links between tumour metabolism and underlying genotype/microenvironment. This research will enable us to target the metabolic pathways evident within brain tumours for therapeutic gain as well as improving our understanding of how tumour metabolism responds to stress in the tumour microenvironment. We plan to infuse patients with 13C labelled metabolites during their surgery. We then plan to resect the tumour as normal but rapidly freeze samples of tumour for analysis. No extra tumour will be taken as a result of this process. We also plan to derive cell lines from patients entered into this study. This will enable us to generate animal models to test how well these models recapitulate the pattern of heterogeneity extant within the patient. This will also enable us to understand how tumours respond to therapy and microenvironmental perturbation.

  • REC name

    East of England - Cambridge East Research Ethics Committee

  • REC reference

    18/EE/0283

  • Date of REC Opinion

    18 Oct 2018

  • REC opinion

    Further Information Favourable Opinion