Investigation of the role of metabolism in tumorigenesis

Cancer is currently viewed as a genetic disease whereby well-characterised gene mutations are sufficient to drive unrestrained growth and proliferation. In order to support proliferation, cancer cells utilise a specific set of nutrients, among which glucose and glutamine are the most important. It has been shown that inherent dysfunctions of glucose and glutamine metabolism in some circumstances predispose to cancer formation. However, how altered metabolism drives tumorigenesis in not fully understood.
In this programme, we intend to investigate the role of metabolic genes involved in cancer formation using cell culture and animal models. Our goal is to define how each candidate gene triggers tumorigenesis in vivo and to find metabolic pathways required for the survival of these mutant tumours in order to determine potential anti-cancer drug targets. Furthermore, we aim to detect early signs of these metabolic changes in body fluids such as urine and blood, in order to discover novel biomarkers for the early detection of cancer.

In order to proliferate, migrate, and survive under the harsh environmental conditions experienced in solid tumours, cancer cells undergo profound metabolic changes. Oncogenes and tumour suppressor orchestrate this metabolic reprogramming by activating cancer-specific metabolic pathways that optimise nutrients utilisation. The correlation between cancer and altered metabolism is mutual. Indeed, recent evidence suggests that small molecule metabolites accumulated under physio-pathological conditions support and, in some cases, promote cell transformation. These small molecule metabolites, also known as oncometabolites, have been shown to activate oncogenic signalling cascades by impinging on both transcriptional and translational processes in the cell. However, how cancer cells rewire their metabolism and how, in turn, metabolites contribute to tumorigenesis is still unclear.
Our laboratory uses a multidisciplinary approach to understand the intricacies of cancer metabolism and to elucidate novel mechanisms of tumorigenesis driven by metabolic cues, including nutrient and oxygen availability. In particular, our approach encompasses the use of in vitro and in vitro models of cancer, their metabolic characterisation using metabolomics methods, and systems biology to model the results. We aim to exploit this knowledge to find novel pharmacological targets and to discover cancer biomarkers that can be used for early detection and for assessing disease progression. Our work has multiple implications for health and disease. First, it will improve our understanding of the process of cancer transformation, bringing a novel perspective to the field of oncology. Second, our work will investigate synthetic lethal pathways in cancer cell to find novel pharmacological targets for cancer therapy. Finally, by discovering novel biomarkers of cancer, our work will provide the community with tools for early detection of cancer and for patient stratification.