Normal mouse mammary glands and stained glands.

Introduction

Positron emission tomography images of liver tumours in mice showing how they use different amounts of the nutrient glucose.

Positron emission tomography images of liver tumours in mice showing how they use different amounts of the nutrient glucose.

Metabolic changes can make tumour cells selectively dependent upon certain nutrients and metabolic pathways, making tumour metabolism an attractive therapeutic target.

Metabolic changes are thought to provide tumour cells with a proliferation and survival advantage over healthy cells. However, these alterations can also make tumour cells selectively dependent upon certain nutrients and metabolic pathways, making tumour metabolism an attractive therapeutic target.

Both the genetic lesions and the tissue of origin are known to be critical factors that determine tumour metabolism (Figure 1). However, the relationship between these factors and their contributions to the metabolic requirements of different tumour types in the context of the whole organism remain largely unknown and are the focus of our research.

We are employing genetics and stable isotope-based metabolomics approaches to investigate how metabolism is changed in tumours induced by specific pro-tumourigenic events in various mammalian tissues. We are seeking to understand the molecular mechanisms of tissue-specific regulation of metabolic pathways by different oncogenes as well as how oncogenes induce the metabolic dependence of transformed cells in vivo. Finally, we are interested in exploring the relationship between oncogenes and metabolic changes in various types of human cancers.