29 May 2009

Exposure to "secondary genes" – a new approach to cancer treatment?

Scientists have found weaknesses of mutant cells that cause cancer
RIA News

Scientists have found weaknesses of cancer cells responsible for the most hopeless and untreatable forms of cancer, which may lead to the emergence of a new generation of anti-cancer drugs of selective action, safe for healthy tissues, according to two research papers published in the journal Cell.

The authors of the publications studied cancer cells carrying mutations in a gene called KRAS by scientists. This mutation leads to such severe forms of cancer as various forms of leukemia, lung and stomach cancer, which practically cannot be treated with selective anticancer drugs and require the use of techniques that negatively affect healthy body tissues.

"This mutation has put us in a very awkward situation when, knowing the causes of the disease, we can't do anything about it," said Gary Gilliland, the lead author of one of the publications from Harvard Medical School, quoted by the press service of the Cell Press publishing house.

Most targeted anticancer drugs are directed directly at the genes that cause cancer, but this approach is not always effective.

The authors of the studies drew attention to the fact that in the process of their development, cancer cells produce so-called secondary dependencies in relation to the work of other genes that do not cause cancer by themselves. Disorders in the work of these "secondary" genes can be fatal for cancer cells, which can be used.

"Cancer cells are not at all some kind of "supercells", as many believe. In fact, these are diseased cells whose vital activity is determined by a large number of compromises, which in turn can be used to fight cancer," said Stephen Elledge, lead author of the second study.

Instead of trying to somehow influence the work of the KRAS gene, the authors of the studies tried to find out which genes determine the survival of cancer cells carrying a similar mutation.

To do this, Gilliland's group applied the technology of highly efficient RNA interference, during which a large array of short RNA fragments is used, significantly reducing the activity of certain genes in DNA.

Thus, a group of scientists studied the entire human genome, during which they found many genes on which the vital activity of cancer cells depends. More than the rest, the attention of scientists was attracted by the gene responsible for the synthesis of the enzyme PLK1. This enzyme belongs to the class of so-called kinases, which are good targets for selective drugs.

Clinical practice shows that patients with delayed functioning of this gene survive as a result of treatment more often than others, and therefore it can be a "target" for new anti-cancer drugs.

The second group of scientists led by Elledge focused on studying only the genes encoding kinases using RNA interference. The authors of the work managed to show that cancer cells with a KRAS gene mutation are very sensitive to the suppression of STK33 kinase activity.

"The strategy of influencing cancer cells through secondary genes is very promising, since, for example, in order to destroy a cancer cell, we need to reduce the activity of the STK33 gene by only 50-70%, and normal cells do not have such weakness, and therefore in this case will remain unaffected," Gilliland said.

According to the authors of the research, such work may in the future lead to the creation of combined anti-cancer drugs, the action of which will be based on the suppression or activation of several genes in DNA at once, on the work of which cancer cells depend.

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