Hutchison/MRC Research Centre

Most common cancers are difficult to treat successfully once the cancer has spread. Scientists at the MRC Cancer Cell Unit in the Hutchison/MRC Research Centre have identified improved methods to detect cancer early.

A major goal in public health is to detect cancer, or pre-cancerous changes, at an early stage using methods that are effective and practical enough to roll out to GP surgeries, medical screening laboratories and developing countries.

‘For cancer of the oesophagus,’ explained Dr Rebecca Fitzgerald, ‘most patients present with symptoms late on, when they are having trouble swallowing. By then, the chance of surviving five years after therapy is only 20%, and yet the first signs of disease in these patients are often visible 10–20 years beforehand.’

‘Screening for cervical cancer using the smear test is a prime example of the success of early detection programmes,’ added Dr Nick Coleman, ‘but cervical changes are subtle and a high degree of training is needed to recognise them. What’s needed is an effective way of automating screening.’

Professor Ron Laskey and Dr Coleman have discovered a biomarker that enables screening for differences between normal and diseased cells. Normal cells don’t express mini chromosome maintenance (MCM) proteins, whereas cancerous and pre-cancerous cells express them in abundance. Screening for the presence of MCM proteins in cervical smears can substantially improve early diagnosis. The technology has been licensed to Becton, Dickinson and Company, which is running large-scale trials for cervical cancer screening. Meanwhile, the researchers are now investigating the wider application of this tool: in colorectal cancer, in collaboration with Mr Richard Miller, Consultant Colorectal Surgeon in the Department of Surgery, in lung cancer and in anal cancer.

MCM proteins are also being used by Dr Fitzgerald to detect pre-cancerous changes in the oesophagus. Cancer of the oesophagus kills about 7,000 people each year in the UK, and the figure is increasing. Two-thirds of cases develop through a recognisable pre-cancerous stage called Barrett’s oesophagus and Dr Fitzgerald has developed a means of detecting this without endoscopy. A sponge on a string is swallowed and is then gently withdrawn up the oesophagus, bringing with it samples of the lining cells to be examined for evidence of biomarkers. Following the success of a pilot study of 500 patients with a history of heartburn (associated with the development of Barrett’s oesophagus), a much larger study is being planned to see just how accurate the test is in comparison with endoscopy.

Testing positive to early detection tests will define much smaller groups of individuals who can then be offered specialist investigation and treatment at a very early stage of the disease, when the chances of full recovery are high.

For more information, please contact Dr Rebecca Fitzgerald (rcf29@hutchison-mrc.cam.ac.uk) or Dr Nick Coleman (nc109@hutchison-mrc.cam.ac.uk).

The Cambridge Molecular Therapeutics Programme (CMTP) is developing innovative strategies to widen the repertoire of ‘druggable’ cancer targets and accelerate the clinical development of new medicines.

The discovery and clinical development of new medicines against human diseases such as cancer is long, expensive and inefficient. A major problem is that fewer than 10% of the proteins encoded in the human genome have successfully been ‘drugged’ using conventional methods, making it difficult to target those linked with cancer. A second is that the failure rate during early clinical development of new anticancer drugs is unacceptably high, largely due to poor understanding of their effects. The CMTP harnesses the strengths of Cambridge academic sciences to address these key challenges, bringing together expertise in chemistry, structural biology, physics and engineering (led by Professors Chris Abell, Tom Blundell and Mike Payne) with the biomedical research in the Hutchison/ MRC Research Centre led by Professor Ashok Venkitaraman.

New approaches to widen the repertoire of ‘druggable’ targets start with the development of novel assay platforms to identify the hard-to-find targets that characterise different forms of cancer. A platform of innovative screening methods is then used to discover chemical ‘leads’ that can be used against them. These include fragment-based methods, where small fragments (rather than complete drug molecules) are soaked into crystals of the target protein to identify the site and nature of the binding interaction, and this information is used in the design and synthesis of the next generation of inhibitors. Another approach involves novel ‘libraries’ of drug-like chemicals, which are screened for activity against target proteins by biophysical assays, cell-based assays and in silico screens, and elaborated further using structure determination

The second major strand of work in the CMTP is to accelerate the early clinical development of new anticancer drugs through improved understanding of their effects on normal and cancer cells. Several new approaches are being taken, including the establishment of laboratory models that more accurately predict the effects of drugs on human cancers, and methods to screen for biomarkers that determine which patients are most likely to benefit from the drugs. This work has already led to the design of new types of clinical trials that more effectively match the right drugs to the right cancer patients.

Early success in developing these new approaches has secured over £6 million in funding for the CMTP from sponsors including the MRC and the Wellcome Trust.

For more information about the CMTP, please visit the CMTP website or contact Professor Ashok Venkitaraman (arv22@hutchison-mrc.cam.ac.uk), the Ursula Zoellner Professor of Cancer Research.