Clinical and Translational Research in Gastrointestinal Cancer We aim to exploit and maximise the benefits of anti-cancer drug therapies for patients with the common digestive tract cancers such as bowel, stomach, gullet and pancreas cancer.
Our approach is to run an integrated programme of large clinical trials testing new drugs (or new methods of using older drugs), and at the same time to perform “translational” laboratory research using samples donated by the trial patients (Figure 1). This is allowing us to identify proteins and genes which correlate with the benefits or side-effects of specific drugs for individual patients. The eventual goal of this research is “personalised medicine”, that is, selecting for each individual patient the drug or drugs which have the best chance of helping them and the least risk of causing harm.
To perform the large clinical trials necessary for this work, we collaborate with clinicians all over the UK and abroad. Our recently-completed trials include “FOCUS” which, with 2135 patients, is the largest ever reported in advanced bowel cancer, and “FOCUS-2” a trial defining the best treatment options for frail, elderly patients. We are currently leading and co-developing many more trials, together involving several thousand patients.
All these trials include translational research. In FOCUS, we have already shown that some patients’ tumours contain high levels of a protein, Topoisomerase-1, and that for these patients the early use of the drugs irinotecan or oxaliplatin may substantially improve their survival (Figure 2). This and many other findings are being further explored in our ongoing projects.
Figure 1. A Tissue Microarray. Cylindrical tumour cores 0.6mm in diameter from many different patients are aligned in a single paraffin block. When sliced, many patients can be analysed simultaneously.
Figure 2. For patients with advanced bowel cancer, survival time may be limited. Our “FOCUS” trial showed that patients with “high-Topo1” cancers may benefit from specific drug treatments.
Seymour MT, Maughan TS, Ledermann JA, et al. Different strategies of sequential and combination chemotherapy for patients with poor prognosis advanced colorectal cancer (MRC FOCUS): a randomised controlled trial. Lancet 370: 143-52, 2007
Braun MS, Richman SD, Quirke P, Daly C, Adlard JW, Elliott F, Barrett JH, Selby P, Meade AM, Stephens RJ, Parmar MK, Seymour MT. Predictive biomarkers of chemotherapy efficacy in colorectal cancer: results from the UK MRC FOCUS trial. J Clin Oncol 26: 2690-8, 2008
Hennig IM, Naik JD, Brown S, Szubert A, Anthoney DA, Jackson DP, Melcher AM, Crawford M, Bradley C, Brown JMB, Seymour MT. Severe sequence-specific toxicity when capecitabine is given following fluorouracil and leucovorin. J Clin Oncol 26:3411-17, 2008.