Cancer

The late Sir Richard Doll helped save millions of lives by demonstrating that smoking greatly increased the risk of getting cancer (and many other diseases) and that stopping smoking worked remarkably well. His colleagues Professors Valerie Beral, Zhengming Chen, Rory Collins, Sarah Darby, Tim Key and Sir Richard Peto, all in the Richard Doll Building, are continuing to save lives by conducting large prospective studies of smoking, drinking, diet, obesity, hormone replacement therapy and other avoidable causes of cancer. These studies are being conducted among millions of people throughout the world. They also conduct worldwide meta-analyses that combine hundreds of different studies of cancer causes, early detection, or treatment – showing, for example, that breast cancer mortality can generally be halved by combining radiotherapy, chemotherapy and hormone therapy.

Elsewhere in Oxford, Professor Peter Donnelly led a consortium that found genetic risk factors for breast cancer; Professor Adrian Harris pioneered drug therapies based on blocking the blood supply to tumours – now accepted as an effective strategy; and Professor Herman Waldmann developed a monoclonal antibody therapy, Campath-1H, which is on the market as a treatment for chronic lymphocytic leukaemia.

These highlights of Oxford’s involvement in cancer research in recent decades bode well for the future. Through strategic appointments, the University has built a critical mass of epidemiologists, trialists, geneticists, and other cancer researchers.

The new Institute of Cancer Medicine houses key teams in clinical pharmacology, cell biology, and radiation oncology and biology. It provides the nucleus for a network embracing researchers across the University with an interest in cancer. Clinical pharmacologists such as Professor Nick La Thangue are working to identify specific biomarkers that will reveal whether or not a particular tumour is sensitive to a particular drug. Professor Gillies McKenna, recruited to head the radiation oncology and biology team after a 30-year career in the US, says that Oxford is now unique internationally in the cancer field: ‘There’s no other centre of this size and scope.’ His team is looking for pathways that increase or decrease the cell’s resistance to radiation.

In developing new treatments the watchword is translation: how can research results be applied as better care for patients? One example is a collaboration between doctors and engineers at the Oxford Institute of Biomedical Engineering, conveniently housed in the same research building as the Institute of Cancer Medicine. High-intensity focused ultrasound (HIFU) is a novel technique that can be used to destroy deep-seated tumours non-invasively, and the Churchill Hospital became home to the very first clinical HIFU Unit in the western world in 2002, with a second unit now under construction in the new clinical Cancer Centre. In collaboration with urologists Mr David Cranston and Mr Tom Leslie, Dr Constantin Coussios and his research team are developing novel strategies for the improved delivery and real-time treatment monitoring of HIFU therapy, by exploiting the tiny gas bubbles generated spontaneously by the ultrasound wave as it travels through the body. These bubbles act both as promoters and as markers of treatment, because they accelerate ultrasound-induced heating of the tumour and can be readily imaged using novel ultrasound-based imaging strategies developed within the Institute of Biomedical Engineering.

Meanwhile, basic cancer researchers are capitalising on the rapidly increasing understanding of the molecular signals that control the cycle of cell life and death, and how these are disrupted in cancer. Professor Xin Lu, who has brought the Ludwig Cancer Institute's UK laboratory to Oxford, is looking for ways to reactivate one of the cell's built-in tumour suppressors. This tumour suppressor is lost or inactive in almost all human cancers, and a better understanding of it could lead to the development of strategies to kill cancer cells selectively. Professor Colin Goding, Dr Gareth Bond and Dr John Christianson have also recently joined the Institute. They are studying gene expression in stem cells and melanoma, analysis of genetic variants and their effects on cancer, and protein degradation in an area of the cell called the endoplasmic reticulum.

Over the past 20 years Britain has seen the biggest decreases in the world in national rates of death before age 70 from lung cancer and breast cancer (which are both down by half) and cancer in general (which is down by almost one third). Still, however, two-thirds of the risk remains, and Oxford scientists are well placed to help the current revolution in the multi-disciplinary effort that is cancer research to yield new causes and new cures.