The Institute of Cancer Therapeutics
Scientific Overview 2006/7

In 2006 the YCR programme grant awarded to Professor Laurence Patterson became fully operational with the recruitment of three medicinal chemists and a proteomics specialist all contributing to the cancer medicines discovery at the Institute of Cancer Therapeutics as outlined below. The YCR chemistry team is responsible for a group of postdoctoral chemists, PhD students and a technician all funded from resources secured as a consequence of the core YCR support. Additionally in September 2006 the YCR Cancer Medicines Discovery facility was relocated to a purpose-built new building ion the UoB main campus. The new and expanded YCR medicinal chemistry facility is fully operational and has allowed the preparation of compound libraries that are under investigation as potential new cancer treatments.

New drugs that specifically starve the cancer of food
The principle investigator Prof Laurence Patterson in collaboration with Dr Robert Falconer, a YCR funded research lecturer in medicinal chemistry is harnessing the use of Matrix metalloproteinases (MMPs) that are known to be expressed in the tumour. MMP’s are a family of proteases that are essential for the development of the tumour blood supply and tumour spread. We have made a new type of treatment that is inactive in normal tissues but in the cancer environment releases a drug that can shut down tumour blood vessels. In collaboration with Dr Jason Gill and Dr Paul Loadman at the Institute we are exploring the benefit of these agents in tumour models with the aim of proving their value for clinical use.

A ‘spoonful of sugar’ to stop tumour spread
Metastasis, the process where tumours break up and travel to distant parts of the body, is the main cause of death in cancer patients. On the surface of cancer cells there is a sugar polymer, polysialic acid, which has been found in a large number of different tumours. When cancer cells start to spread, they appear to get more polysialic acid on their surface and it has been suggested that this helps these cells ‘unstick’ so they can start invading the surrounding tissues and moving away from the original tumour. It is our working hypothesis that polysialic acid has a crucial role in tumour spread. Prof Patterson with Dr Falconer (YCR lecturer) and Dr Afarinkia (YCR Senior Lecturer) are devising molecules that should inhibit the formation of PSA and hence prevent tumour spread. Biological techniques and chemical probes synthesised as part of this project are under way to establish the validity of our approach. This project particularly illustrates the value of inter-institutional collaborations. Our drug design is informed by molecular modelling in collaboration with Dr Colin Fishwick (University of Leeds). In collaboration with Prof Paul Smith (University of Cardiff) we are investigating the effects of our agents directly on cell-surface polysialic acid. With Dr Paul Loadman at the Institute and Prof Minota Fukuda, (Burnham Institute, USA) we are developing methods to measure the effect of our new molecules on polysialic acid decoration. If successful sugar-based drugs may well be the answer to preventing the spread of certain types of very aggressive tumours. A spoon-full of sugar may be the answer!

A biological blow torch to treat cancer
Professor Laurence Patterson and Dr Klaus Pors (YCR lecturer) are harnessing a protein family (called cytochrome P450) that are highly abundant in cancer cells and can ‘weld oxygen’ onto chemical agents. This process can convert otherwise inactive compounds to highly toxic and tumour selective cancer medicines. Agents are currently prepared that are undergoing evaluation in collaboration with the biology team at the institute. Dr Thomas Friedberg at Dundee University is collaborating to identify a gene therapy approach that might also make use of the agents we have invented.

Low oxygen in cancers for tumour-selective medicines
Solid tumours account for 90% of all human cancers and despite their rapid growth they can harbour poorly oxygenated regions. There is strong evidence that these low oxygen regions are associated with tumour resistance to radiation and drug treatment in the clinic. The importance of cell killing in those regions of tumours with low oxygen tension (hypoxia) is crucial if cancer is to be effectively treated. Prof Laurence Patterson with Dr Klaus Pors (YCR lecturer) are developing agents that are activated selectively in the hypoxic tumour environment. This is building on the success to date of AQ4N, invented by Prof Patterson as a tumour hypoxia-selective cancer drug presently in worldwide Phase I and II clinical trials undertaken by Kudos Pharma and Novacea Inc. The new approach is in recognition of the major clinical use of alkylating agents to treat cancer despite their general chemical reactivity and hence toxicity to normal tissues. Prof Patterson and Dr Pors have designed alkylating agents that are not toxic until converted, in hypoxic tumours, to highly reactive and tumour killing alkylating agents.

Support facility to help medicines discovery

A major instrument with capability to identify hundreds of cancer proteins simultaneously (called proteomics) and funded by YCR and the University of Bradford was made fully operational in April 2006. Prof Patterson and Dr Chris Sutton (YCR Senior Lecturer) are using this state-of-the-art-equipment to help clarify the cancer expression of proteins important in cancer treatment including those identified above. Among other projects this facility is the focus of a project initiated in 2006 in collaboration with Dr. Kyriacos Kyriacou, Cyprus Institute of Neurology and Genetics to facilitate proteomics screening of normal and tumour breast tissues.
 

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YCR science overview 2002/3
YCR science overview 2003/4
YCR science overview 2004/5
YCR science overview 2005/6

Programme of research 2001/2
Programme of research 2002/3
Programme of research 2003/4
No programme of research in 2004/5
Programme of research 2005/6
Programme of research 2006/7

Publications 2001/2
Publications 2002/3
No publications in 2003/4
No publications in 2004/5
No publications in 2005/6
Publications 2006/7

Reports 2001/2
Reports 2002/3
Reports 2003/4
No reports 2004/5
Reports 2005/6
Reports 2006/7

Bradford University cancer site