Early Trials of Cancer Drug Show Promise

Thursday 16 June 2005

Promising results from the UK’s first clinical trial of a prototype cancer drug have raised the prospect of an effective new treatment against a range of cancers, including breast, prostate, bowel, kidney, ovarian and skin cancer.

Published today* (Thursday) the research reveals the drug’s ability to attack cancer cells on a number of fronts at the same time, and gives the first indication that it may have the potential to halt the disease in patients.

The Cancer Research UK funded trial was carried out by Institute of Cancer Research scientists at The Royal Marsden Hospital.  The drug was provided by the National Cancer Institute in the US under a Cooperative Research and Development Agreement with the agreement of US biotech company, Kosan Biosciences Inc.

The research team already knew that the drug – labelled 17AAG - selectively and potently blocks the growth of a wide range of common cancer cells in the laboratory, causing them to ‘commit suicide’.

This new study confirmed that it also works biochemically as intended in patients with a variety of cancer types.  Clinical results in two patients with malignant melanoma provide early evidence that the drug may be able to tackle cancers that are resistant to other drugs.

Further trials, each looking at patients with a specific tumour type, are planned to establish the extent of the drug’s treatment potential in different kinds of cancer. 

The Cancer Research UK funded team is already testing the drug in patients with malignant melanoma, and other teams in the US are looking at patients with prostate, breast and kidney cancer.

The drug works by targeting and inactivating a crucial molecule called Hsp90.  Hsp90 plays an important role in the transmission of messages around the cell by helping to control the structure and function of a large number of other molecules many of which are critical for cancer growth.

Cancer cells are dependent upon these molecules and will die if deprived of them, whereas healthy cells are not seriously affected by their loss.  This makes the new drug highly targeted, as well as deadly, to cancer cells.  The drug simultaneously targets many molecules vital for growth, including proteins, BCR-ABL, c-RAF-1, AKT/PKB, CDK4 and mutant P53.  Using this multi-pronged attack, the drug acts like several different treatments combined, reducing the chances that a tumour will develop resistance.

Different doses of the drug were given to 30 patients with a range of common cancers.  To find out whether the drug hit its target, the team measured the levels of two of the molecules vital for cancer growth – c-RAF-1 and CDK4 – and found that they consistently fell in response to the drug.  By careful monitoring of the patients’ progress over time, the team was able to determine the optimum dose for the drug to act. 

Lead researcher, Professor Paul Workman of the Cancer Research UK Centre for Cancer Therapeutics at The Institute of Cancer Research, says:  “Hsp90 helps to maintain the shape, stability and function of all sorts of important molecules, a large number of which play critical roles in the development of cancer.  The results of this research suggest that, by blocking the action of Hsp90, the drug has the potential to attack cancer by shutting down a range of systems that cancer cells use to grow and spread.”

Professor John Toy, Cancer Research UK’s Medical Director, says:  “These results, are very early and, although encouraging, much more work to assess the drug’s effect in large numbers of patients still needs to be done.  However, what’s particularly exciting about this drug is that it targets so many different features of cancer’s machinery all at once, which should make it much more difficult for tumours to develop resistance to treatment.”

Professor Peter Rigby, Chief Executive of The Institute of Cancer Research, says: “This early trial indicates the potential of this drug for future cancer treatment. Although further trials need to be conducted, early indications suggest that the multi-pronged attack by this drug shows promise in treating a range of cancers."

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For more information, or to arrange interviews, please contact:

Cancer Research UK

Sophy Gould on 020 7061 8318 or, out-of-hours, the duty press officer on 07050 264 059.

Notes to editors

• *Journal of Clinical Oncology.
• "A phase I pharmacokinetic (PK) and pharmacodynamic (PD) study of 17- allylamino, 17-demethoxygeldanamycin (17- AAG) in patients with advanced malignancies"
• Udai Banerji, Anne O'Donnell, Michelle Scurr, Simon Pacey, Sarah Stapleton, Yasmin Asad, Laura Simmons, Alison Maloney, Florence Raynaud, Maeli Campbell, Michael Walton, Sunil Lakhani, Stanley Kaye, Paul Workman, and Ian Judson 
• The Trial/The drug (17AAG) was administered intravenously once a week without a break.
• Patients with the following types of cancer took part in the trial: melanoma, sarcoma, breast, colon, mesothelioma (cancer of the mesothelial cells that cover the outer surface of most internal organs of the body), ovarian, renal, non-small cell lung cancer, pancreatic, primary peritoneal (cancer of the peritoneum – the membrane that forms the lining of the abdominal cavity), parotid (cancer of the salivary glands), and unknown primary (cancer that has started in an unknown part of the body).
• For more information about different types of cancer, diagnosis and treatment for patients and their families, visit Cancer Research UK’s patient information website www.cancerhelp.co.uk.
• Hsp90/Hsp90 is a chaperone protein and has the job of ensuring that molecules within the cell are folded into the correct shape.  Protein molecules are made up of long strips of amino acids, carefully folded into particular three-dimensional structures. 
• Incorrect folding will stop a molecule from working and may lead to its breakdown by the cell’s mechanisms that are constantly on the lookout for molecules that are damaged or defunct.
• When inactivated, Hsp90 can no longer keep other molecules within the cell in their correct shape, causing some to lose their activity and others to be broken down or removed.
• Cancer Research UK

- Cancer Research UK's vision is to conquer cancer through world-class research

- The charity works alone and in partnership with others to carry out reseach into the biology and causes of cancer, to develop effective treatments, improve the quality of life for cancer patients, reduce the number of people getting cancer and to provide authoritative information on cancer. Cancer Research UK is the world's leading independent charity dedicated to research on the causes, treatment and prevention of cancer.

- For further information about Cancer Research UK's work or to find out how to support the charity, please call 020 7009 8820.

- For further information about Reduce the Risk please visit www.reducetherisk.org.uk.

• The Institute of Cancer Research and The Royal Marsden Hospital

- The Institute of Cancer Research works in a unique partnership with The Royal Marsden Hospital, forming the largest comprehensive cancer centre in Europe, with more than 40,000 patients being seen at the hospital's sites in Chelsea and Sutton each year. This relationship enables us to stay in close daily contact with those on the frontline in the fight against cancer- the clinicians, the carers and most importantly, the patients.

- 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. The Institute is unrivalled in its record of cancer drug discovery and development.

- For more information, log on to www.icr.ac.uk, or contact The Institute of Cancer Research on 0207 153 5542, or email [email protected]