Perturbation of metabolic changes in solid tumours to effect therapy
Solid tumours are hungry tissues with an elevated metabolic demand. However, their hostile local microenvironment and the chaotic 3-D organisation renders conventional bio-energetic metabolism inefficient to meet cellular need. Consequently, solid tumours undertake considerable adaptive changes to their bioenergetic spectrum. Our team is in the process of generating a comprehensive characterisation of bio-energetic strategies within solid tumours.
The focus of this project will be to utilise the above information to develop novel therapeutic strategies. We propose to perturb some of the 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.
For a description of the solid tumour model and its use please see the following articles
- Mellor, H. R., Snelling, S., Hall, M.D., Modok, S., Jaffar, M., Hambley, T.W. and Callaghan, R. (2005). The influence of tumour microenvironment factors on the efficiency of cisplatin and Pt(IV) complexes Biochemical Pharmacology 70, 1137-1146.
- Mellor, H. R., Ferguson, D. J. P., and Callaghan, R. (2005). A model of quiescent tumour micro-regions for evaluating multicellular resistance to chemotherapeutic drugs Br J Cancer 93, 302-309.