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. 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 US biotech company, Kosan Biosciences Inc.
The research team already knew that the drug - labeled 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 tumor 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 tumors to develop resistance to treatment."
SOURCE:
Cancer Research UK (http://www.cancerresearchuk.org)
