Adaptations of solid tumours to their environment

Perturbation of metabolic changes in solid tumours to effect therapy

Solid tumours are hungry tissues with an elevated metabolic demand. Moreover, solid tumours must adapt and respond to the hostile local microenvironment and their chaotic 3-D tissue organisation. The cellular changes used in these adaptations renders conventional bio-energetic metabolism inefficient to meet demand. Consequently, solid tumours remodel how they utilise fuels such as glucose, glutamine, protein and lipids for cellular function. The two main purposes for these fuels are (a) to generate energy in the form of ATP and (b) to provide sufficient biomass to enable cell division. The adaptations in fule utilisation must maintain the delicate balance between these two purposes.

Our laboratory has characterised the cellular adaptations using several models of solid tumours. This information can now be used to develop novel therapeutic strategies against solid tumours. In particular, we propose to perturb several metabolic adaptations to ascertain whether these generate an Achilles heel for the tumour. The investigations will be undertaken using the spheroid and multicell layer models of 3-D tumours and a variety of reporter assays including flow cytometry, spectroscopy (colorimetric and fluorimetric), chromatography and microscopy. For a description of the solid tumour model and its use in tumour biology please see the following articles from the host laboratory