IF IT happened in a factory, it would be condemned as industrial sabotage. But in the battle against cancer, a molecule that wreaks havoc on the protein assembly line is just what is needed. Now a drug that does this is showing early promise, extending one skin cancer patient鈥檚 life by four years after other treatments had failed.
The drug, known as 17AAG, renders several key signalling proteins useless. Because cancer cells are actively growing and dividing all the time, the ability to manufacture these proteins is much more important than for normal cells.
The drug, which is made by Kosan Biosciences of Hayward, California, is one of a new generation of anti-cancer agents designed to disable the life-support systems of cancerous cells. 鈥淚t has an effect on multiple cancer proteins,鈥� says Paul Workman of the Institute of Cancer Research in London, run by the charity Cancer Research UK. It works by disrupting heat shock protein 90 (Hsp90), a 鈥渃haperone鈥� molecule that helps to fold newly formed proteins into the correct shape.
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The list of proteins disabled as a result reads like a rogues鈥� gallery, as many of them are known to be involved in cancer. Most are signalling proteins, such as c-RAF-1 and CDK4, which are often permanently switched on in cancer cells, telling them to carry on multiplying. 鈥淐ancer cells have greater dependence on these proteins, so when you take them away, they can鈥檛 cope any more,鈥� says Workman.
His team gave 30 patients weekly injections of 17AAG for three months or more. The patients had a range of advanced cancers for which all other treatments had failed. Of the 11 people with malignant melanoma, an aggressive form of skin cancer, two survived for much longer than expected 鈥� one for 15 months and one for four years. 鈥淭he cancer didn鈥檛 go away, but it didn鈥檛 progress,鈥� says Workman, whose team鈥檚 results appear in the Journal of Clinical Oncology (vol 23, p 4152).
Analyses of biopsies and blood samples showed that the drug was working as planned in most patients, even if they did not all survive as long. So by tweaking the dose and the molecule itself, it might be possible to treat many types of cancer, says Workman.
Parallel trials against several types of cancer including breast, prostate and kidney are under way in the US, overseen by the National Cancer Institute in Bethesda, Maryland. Another version of the drug is under development at Conforma Therapeutics in San Diego, California.
The drug appears to be safe at the dosages used, but there are potential dangers. 鈥淚f you inhibited Hsp90 completely, patients would die,鈥� says Pramod Srivastava of the University of Connecticut Health Center in Farmington, who studies the protein. 鈥淏ut maybe there鈥檚 a window of dosage where the treatment kills the cancer, not the patient.鈥�
