Colon and Lung Cancer Research

Colorectal and lung cancers are among the most common malignancies. We are identifying new biomarkers of prognosis and therapeutic responsiveness, in order to improve the clinical management of cancer. We aim to understand how and why cancer develops and how it should be best treated. This work involves three main approaches (1) study of cancer specimens from patients (2) analysis of cancer cells grown in cell culture and (3) study of tumours in the mouse.

In colon cancer, we focus on the tumour suppressor gene MCC, which had been overlooked until we showed that it is epigenetically silenced in up to 50% of sporadic and inflammatory bowel disease (IBD)-associated colorectal cancers. Since then, we and others have described several new molecular functions for this protein which explain its role in tumour suppression and therapy responsiveness. MCC is emerging as an important multifunctional protein that regulates several cellular processes.

In rectal cancer, we study the molecular basis of chemoradiotherapy (CRT) responsiveness using Whole Genome Sequencing and aim to develop a diagnostic test. Rectal tumours can respond well to CRT, with a remarkable complete healing response in ~20% of patients. On the other hand, about 25% or rectal cancers show complete resistance to CRT. The reason for such variability is unknown and currently there is no routine diagnostic test to determine who is likely to benefit from receiving this treatment.

We also study colon cancer in the mouse and have developed a new model of colitis-associated cancer using the MCC knockout mouse. This model has revealed novel findings about the very early steps of colon carcinogenesis in long-standing chronic IBD and the significance of MCC silencing in these tumours.

In lung cancer we characterise the whole genomic profiles of mutations that occur during carcinogenesis in order to implement the best methods to diagnose these changes in patient tumours.

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