YCR research 2003/4

University of Bradford
YCR Laboratory of Drug Design

The Yorkshire Cancer Research (YCR) Laboratory of Drug Design was established in September 1999 as a core component of the expanding Cancer Research Group (University Cancer Medicine Unit) at the University of Bradford. The principal goal of the laboratory is the rational design and development of new anti-cancer agents for potential use in chemotherapeutic strategies. The Laboratory offers a uniquely focused environment for drug-based chemistry in which to pursue world-class cancer research.

University of Hull
Centre for Magnetic Resonance Investigations

The research portfolio relies on the use of different techniques that reflect the patho-physiological processes associated with tumorigenesis. Alterations in blood flow and volume, vascular permeability, extravascular-extracellular tissue space are examined with dynamic contrast-enhanced T1W imaging; tissue oxygenation studied indirectly using 1/R2; tensor, trace and anisotropic diffusion coefficients of water calculated for tissue differentiation; proton MR spectroscopy studied for metabolite concentrations with particular interest in choline; phosphorus spectroscopy which will provide information on tissue energetics is in development phase; functional imaging is being examined to aid tumour localization with respect to normal at-risk tissues in the brain; and automation of data interrogation is in progress using spatial grey dependence for textural information and neural networks for multi-source data analysis with particular reference to breast imaging.

A multi-technique approach to diagnosis, staging, treatment planning and monitoring of breast, prostate, ovarian and head and neck tumours is in progress. Studies incorporate improved differentiation of benign from malignant lesions and the implementation in routine clinical practice in a multi-centre breast trial; accurate tumour localization for intensity modulated radiotherapy allowing boost dose escalation; early prediction of response to neoadjuvant chemotherapy in both locally advanced breast and ovarian malignancies to allow optimal use of treatment options; and investigation of tissue metabolite concentrations in normal, benign and malignant tissues to aid all phases of patient management.

University of Leeds
Leeds PDT Group

The Leeds photodynamic therapy (PDT) group was founded with YCR support more than 15 years ago. YCR has continued to be the major funder of the group, which is multidisciplinary with many clinicians and scientists working together to bring this emerging approach to more and more patients. Two achievements by the Leeds group have come into particular focus during the past year.

The first is a new approach to the treatment of non-melanoma skin cancer (NMSC), a disease which is on the increase and which affects more than one in four people. The Leeds group was the first in Europe to develop a particular form of PDT using a simple drug known as ALA to treat NMSC. This approach has now spread to many hundreds of centres throughout Europe and many thousands of patients have been treated and cured. The success of this approach has ensured that it has moved into routine clinical practice, and intensive research such as was carried out in Leeds is no longer necessary.

The second achievement is the continued success of the company, Photopharmica, which was founded to commercialise the discoveries made by the Leeds PDT group. The company is now well-advanced with the development of two PDT drugs; one for treating cancer and the other for treating bacterial infections. Indeed, the first patients have now been treated and none of this would have been possible without the YCR support for the Leeds PDT group.

University of Sheffield
The Institute for Cancer Studies and the Development of Clinical Oncology

Cancer research in Sheffield has well-established programmes in both basic and clinical research. Within the YCR Institute for Cancer Studies, Professor Meuth's team is developing leading-edge research into the mechanisms for genetic instability in cancer cells. On the clinical front, there has been further expansion - for example in the fields of clinical trials and bone oncology - and there is also mounting excitement regarding the clinical implications of basic research being undertaken on malignant stem cells.

University of York
The YCR Cancer Research Unit

HRH The Duke of York, KCVO, ADC opened the new laboratories on 23 November 2003. The laboratories are now fully operational and the specialist facilities to generate new viruses capable of targeting prostate cancers for destruction are beginning to prove their worth.

This gene therapy research, established by Yorkshire Cancer Research, has recently been part of a successful 9.7 million Euro bid to the European Community to form a European wide network of laboratories to make prostate cancer gene therapy a reality. In York, genome wide assessments of both gene structure and expression, making use of the information provided by the Human Genome Programme, are being exploited to identify new target genes but also the precise type of cell which needs to be eliminated to prevent recurrence of prostate cancer.
Research on reproductive cancers (including those of the cervix and prostate) has been strengthened by the establishment of a Sexual and Reproductive Health Group (SRHG) under the umbrella of the new Hull York Medical School, which opened its doors to students only last October. While the research in the YCR Cancer Research Unit is of a more fundamental nature, examining the function of specific human papillomavirus proteins, the application of biology to the study of real disease is an important facet of the multi disciplinary group in the SRHG.

University of York
YCR p53 Research Group

Over the past year the Yorkshire Cancer Research p53 Research Group has continued its successful application of a new technology, called RNA interference. This approach allows the selective silencing of cancer-causing genes. Already we have demonstrated silencing of viral oncogenes (human papillomavirus) with consequent killing of cervical cancer cells in culture. Colon cancer cells are destroyed when the Bcl-2 gene is similarly silenced. Clinical development of this exciting new approach to anti-cancer therapeutics requires suitable delivery systems of inducers of RNA interference and this objective is now a major focus of our laboratory.

Studies on the p53 protein are also ongoing, for which purpose we employ techniques ranging from protein expression in insect cells, through engineered protein expression in mammalian cells, to characterisation of naturally expressed p53 protein in human cells. The discovery that endogenous p53 can influence the higher order structure of chromatin and its packaging during cell division has identified new mechanisms by which p53 protects cells from becoming cancerous. It is gratifying that one of the group's publications in 2003 was selected for a News and Views feature in the journal Nature.