genes determining effect of chemotherapy being identified--allowing smaller doses ?
 

Genes control chemotherapy impact

Professor Michael White (right) and a fellow researcher
Scientists have identified key genes which appear to control the impact of chemotherapy on cancer cells.
Researchers from the University of Texas Southwestern Medical Centre systematically blocked the function of individual genes to test their effect.

The Nature study found in 87 cases blocking the gene seemed to boost the impact of chemotherapy.

This could be useful to allow lower chemotherapy doses to be used to reduce side effects for patients.


Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients
Professor Michael White

The researchers used small molecules, called small interfering RNAs, to block the activity of individual genes.

RNA plays a crucial role in converting the genetic DNA code into proteins - but interfering sabotages the process.

After each gene was blocked the researchers tested the survival rate of cancer cells cultured with the chemotherapy drug paclitaxel.

Genome-wide screen

The advantage of the technique is that huge numbers of genes can be tested quickly, as no prior knowledge of the genes involved is required.

In total they tested more than 20,000 genes in this way, using robots to make up the cultures.

Professor White, senior author of the report, said: "The idea of the screen was to be able to take advantage of the new generation of technology to silence any gene we want.

"You go in without any expectations and let the data tell you what's important."

Professor White said some of the key genes identified were not expressed in normal cells.

In theory they could be blocked without any damaging side effects to the patient.

For some genes, blocking drugs already exist and these drugs could be used in combination with chemotherapy to boost its effect.

He said: "Chemotherapy is a very blunt instrument. It makes people sick, and its effects are very inconsistent.

"Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients."

Research needed

However, as the study tested the effects of blocking the genes in isolated human cancer cells, rather than whole animals, more research is now required.

Dr Anthea Martin, science information officer at Cancer Research UK, said: "If this 'gene blocking' technique could be used in patients, it may mean that lower doses of paclitaxel could be given, which would still be effective and reduce side effects.

"However, the study has only looked at isolated cancer cells in the laboratory - this is a great first step, but we don't know if the technique will work in tumours. This will take more research, and we look forward to future developments."