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Gene cluster discovery to aid better cancer therapies

By IANS,

Washington : A promising new discovery of a gene cluster is likely to spur greater understanding of how cancers form and make possible the next generation of effective and user-friendly therapies.

Pinpointing new targets for cancer treatments is as difficult as finding a needle in a haystack, but a University of Rochester team has identified a cluster of 100 multiple genes that cooperate to cause malignant cell transformation.

“We believe that we have found a cornerstone for development of new treatments that ultimately will allow selection of drugs and drug combinations from a pool of compounds directed against these new genes,” said Hartmut Land, lead researcher.

Twenty-five years ago, Land was among the first to discover that malignant cell transformation required multiple mutations in distinct cancer genes. Ever since, he has been studying the cooperative nature of this process and the inner workings of cancer cell function.

His research group began testing, at the genomic scale, a prediction that genes responding synergistically to cooperating oncogenic mutations might act as the “drivers” toward malignancy, Land said. It now appears that this hunch has paid off.

“However, much more work needs to be done to explore how our findings may lead to successful targeting of various cancer types and cancer stem cells,” he said.

Targeted cancer therapy – such as the drug Gleevec that works for patients with certain types of leukaemia and gastrointestinal tumours – is based on a keen understanding of the architecture of cancer.

Much has been learned in the past several years, but what has been lacking is a clear roadmap leading to dozens of new molecular targets.

The researchers found that among 30,000 cellular genes, only about 100 genes responded synergistically to the combination of two of the most prevalent cancer genes, Ras and p53, and were expressed differently in normal and cancer cells.

Ras and p53 are implicated in about half of all cancers.

When p53, a tumour-suppressor gene, loses its function, and when Ras becomes hyperactive, both genes play major roles in promoting uncontrolled growth of colon, pancreas and lung cancers.

These findings have been published online in the journal Nature.