Our aim is to understand the role and significance of genetic alterations that occur in cancer (in particular colorectal and oesophageal cancers) using systems biology.
Our research builds upon the idea that cancer results from a systemic cellular perturbation and, although genes involved in cancer (i.e. cancer genes) differ functionally, they share intrinsic properties that are not visible when studying each gene individually.
We therefore use systems biology approaches to characterise cancer genes in the context of genome and network evolution. For example, we have shown that cancer genes encode highly connected and central proteins of the protein-protein interaction network. We also observed that tumour-suppressors are basic and ancient genes that maintain a single-copy status throughout evolution. Most oncogenes instead originated in metazoans, acquired additional copies in vertebrates and their dosage is often controlled at the post-transcriptional level.
While we continue to characterise new properties of cancer genes, we also use them to (1) identify novel and patient-specific cancer genes; (2) predict the onset of somatic dependencies and vulnerabilities that can be exploited in therapy; and (3) assess the role of clonal and sub-clonal mutations in cancer evolution.
Systems-level properties of known and candidate cancer genes can be found in the Network of Cancer Genes, a public resource that we manually curate and maintain.
Our research is funded by Cancer Research UK (Programme Foundation Award); the Cancer Research UK KHP centre; and the European Union H2020.