Scientists Reveal First Ever Complete Structure of Crucial Anti-Cancer Drug Target
19th April 2006
Scientists at The Institute of Cancer Research today reveal the molecular structure of HSP90, one of the most exciting new anti-cancer drug targets, which may greatly help in developing targeted treatments for a range of cancers including: prostate, breast, bowel, ovarian and kidney.
This is the first time the complete structure of HSP90 has been revealed. The breakthrough shows exactly how this protein works in cells and, more importantly, how it can be stopped by anti-cancer drugs.
HSP90 is a protein found in all cells and is vital for helping other proteins fold into their correct shape. However, cancer cells are especially dependent on HSP90, therefore molecules which block this protein kill cancer cells but have little effect on normal cells.
The team, led by Professor Laurence Pearl, used X-ray crystallography to determine the structure of the protein. The results are published today in Nature*.
Professor Laurence Pearl said: “Due to the very mobile structure of the HSP90 protein and the number of different shapes it adopts, crystallizing it and determining its structure has been a huge challenge which has taken us 10 years. We are now able to see exactly how it works and, most importantly, how to prevent it working. As HSP90 is required to fold proteins involved in many different types of cancer, drugs which target HSP90 hold real promise to treat a number of different cancers.”
The work was funded by The Wellcome Trust and benefits from the infrastructure support at The Institute of Cancer Research from Cancer Research UK.
A number of drugs which specifically target the HSP90 protein in cells – known as HSP90 inhibitors – are currently in development. One of the drugs, known as 17AAG, is currently in phase II clinical trial for patients with malignant melanoma – the most deadly form of skin cancer. A number of others are currently in development in the laboratory and are likely to benefit from this discovery.
Professor Peter Rigby, Chief Executive of The Institute Cancer Research commented: “We are constantly looking for new ways to target cancer cells which will ultimately improve treatments, reduce side effects and enhance patient quality of life. Drugs which target HSP90 are proving to be a very exciting set of anti-cancer drugs in the laboratory and in the clinic. They selectively kill cancer cells so are likely to have fewer side effects than conventional treatments.”
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The Institute of Cancer Research.
- The Institute of Cancer Research is Europe’s leading cancer research centre with expert scientists working on cutting edge research. It was founded in 1909 to carry out research into the causes of cancer and to develop new strategies for its prevention, diagnosis, treatment and care. Website at: www.icr.ac.uk.
- The Institute works in a unique partnership with The Royal Marsden NHS Foundation Trust, forming the largest Comprehensive Cancer Centre in Europe. This relationship enables close daily contact with those on the frontline in the fight against cancer - the clinicians, the carers and most importantly, the patients.
- The Institute is a charity that relies on voluntary income. The Institute is one of the world’s most cost-effective major cancer research organisations with over 90p in every £ directly supporting research.
- The Wellcome Trust is the most diverse biomedical research charity in the world, spending about £450 million every year both in the UK and internationally to support and promote research that will improve the health of humans and animals. The Trust was established under the will of Sir Henry Wellcome, and is funded from a private endowment, which is managed with long-term stability and growth in mind.
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