Colorectal cancer is the third most common cause of cancer related mortality in the UK. More advanced disease often requires additional therapy to control it and acheive optimal rates of cure. What is particularly concerning is that rates of younger onset cancer (diagnosis under 50 years old) are increasing quickly, with no clear cause. These patients more commonly present with advanced disease. In rectal cancers, pre-operative therapy with DNA damaging agents such as platinum-based chemotherapy and radiotherapy are commonly used in patients with more advanced disease.

We have an academic interest in three principal aspects of locally advanced rectal cancer.

BCL-3 and NF-κB signalling in DNA damaging therapy response

Firstly, we want to understand how the pro-inflammatory signalling pathway NF-κB regulates therapy response using in-vitro 2D and 3D models of colorectal cancer. We are particularly focused on a protein called BCL-3, which is known to act as a co-regulatory protein in the NF-κB signalling pathway, and how it regulates the DNA damage response in colorectal cancer cells.

The rising incidence of young-onset colorectal cancer

Secondly, with collaboration with consultant clinical colleagues (Mr David Messenger and Mr Michael Thomas Consultant Colorectal Surgeons) at University Hospitals Bristol and Weston we aim to determine the demographic changes in colorectal cancer incidence over time and use this to generate hypotheses and inform our in-vitro research. This work has shown significant increases in the age-specific incidence of colorectal cancer from around 2006 onwards. The increase is particularly observed in distal tumours (tumours arising in the sigmoid, recto-sigmoid or rectum) with no apparent differences seen between genders, socioeconomic status or ethnicity. Tumours in this age group are far more likely to present with advanced disease (advanced T-stage, nodal disease or metastasis). Future work aims to define differences in management of these patients between older and younger onset patients, in collaboration with Leeds, Oxford and Liverpool.

Sequencing of circulating tumour DNA in Rectal cancer - SectR

Finally, we aim to better measure the response of locally advanced rectal cancers to neo-adjuvant therapy. Despite improvements in imaging and clinical assessment, determining whether patients have undergone a complete or incomplete response to therapy is challenging. We aim to utilise circulating tumour DNA to better define therapy response and enable more personalised treatment decisions to be made for each patient.