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Identifying cancer genes – Will it really lead to better treatment?

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www.ProHealth.com • September 23, 2003


Copenhagen, Denmark: A systematic trawl through the human genome looking for the abnormalities that drive cancer is already producing promising results, a scientist told ECCO 12 – The European Cancer Conference in Copenhagen today (Tuesday 23 September).

Dr. Michael Stratton, Director of the Cancer Genome Project at the Wellcome Trust Sanger Institute, Cambridge, UK, described how his study of the BRAF mutation could provide new targets for drug development, which could lead to better targeted – or even individualised - treatment for cancer patients.

The decoding of the human genome has allowed scientists to compare the normal DNA sequence with that seen in cancers, and hence identify abnormalities. The BRAF mutation is implicated in a number of common cancers, according to Dr. Stratton. It appears to be involved in the switching mechanism of the gene, and is found in 70% of melanomas, in 30% of some types of thyroid and ovarian cancer, and in 10% of colorectal tumours.

Over 80% of the mutations bring about a single change in an amino acid, making it a relatively simple target for rectification. "Once we can identify this kind of abnormal biological process", said Dr. Stratton. "we can move on to the next stage – developing drugs to prevent or correct it."

The traditional approach to research in cancer has been the comparison of treatments through randomised clinical trials, with the extrapolation of an average benefit to the individual. This often means that many patients are inefficiently treated, while only a few benefit. Gene targets herald a different approach, and are becoming increasingly important in the search for effective cancer treatments.

Genes are implicated in cancer in a number of ways – as oncogenes, which drive cancer forward, as tumour suppressor genes that slow down cell division, and as DNA repair genes, which help to keep chromosomes intact when genetic mutation occurs.

A small number of drugs targeted at mutated cancer genes have already been shown to act effectively. "Undoubtedly, these advances have changed the way we think about cancer drug development. BRAF is a promising target and we have initiated a program of drug development targeted at this gene. Early lead molecules have already been found and are now being developed further," said Dr. Stratton.

"However, we must temper our general optimism with caution. We still have much to learn about this new strategy of targeting drugs at abnormal cancer genes. Moreover, drug development is a slow process that can take more than a decade before clinical trials are completed and the effectiveness of the drug is finally known," he said.



Abstract no: 355 (Tuesday 23 September, 14.15 hrs CET, Oncogenomics – biological insights and clinical applications session).



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