A set of genes that can make cancer cells 1,000 times more sensitive to chemotherapy has been identified by scientists, promising a new way of treating tumours with fewer side-effects.

The research in the United States suggests that it will be possible to target cancerous tissue with drugs much more efficiently than is now possible, so that healthy cells are not harmed, and patients are spared the debilitating impact of treatments.

Although chemotherapy can be highly effective, it is generally toxic to the rest of the body as well as to cancer cells, causing serious side-effects. These include nausea and vomiting, hair loss, liver and kidney problems and sometimes permanent damage to fast-growing cells, such as those in the reproductive system.

This has led scientists to seek ways of refining drugs so that they home in on cancer cells, leaving healthy tissue intact, and of reducing the doses at which they can be effective. In the new study, a team led by Michael White, of the University of Texas Southwestern Medical Centre, in Dallas, used a new technique to screen more than 20,000 genes in human lung-cancer cells, to pick up those that appear to be involved in sensitivity to a frontline chemotherapy drug, paclitaxel or Taxol.

They identified 87 genes that made tumours more susceptible to the drug when their activity was blocked or reduced. When some of these genes were silenced, the cancer cells were killed or weakened by doses of paclitaxel 1,000 times lower than normally required.

The findings, which are published in the journal Nature, suggest that it should be possible to use the genes to target cancer cells with paclitaxel more precisely, reducing the amount given to patients.

The drug’s side-effects include nausea, loss of appetite, thinned hair and joint pain.

Dr White 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.”

There are two ways in which the discoveries could be significant. The most likely possibility would be to screen a patient’s cancer for specific genes that make it more sensitive to particular drugs, which would then be administered in low doses. In the longer term, these genetic insights could also inform the design of new cancer drugs, which silence critical genes within cancer cells to make them more vulnerable to chemo-therapy.

In a separate study, also published in Nature, scientists have uncovered new genetic clues to the way breast cancer spreads through the body to the lungs. A team led by Joan Massagué, of the Memorial Sloan-Kettering Cancer Centre, New York, implanted human breast-cancer cells into mice and found that abnormal activity in four genes appears to drive their spread to the lungs. When the genes were knocked out using a technique called RNA interference, the tumour cells’ ability to spread from mouse mammary glands to the lungs was significantly reduced.

- A lack of regular smear tests is the most common contributing factor to the development of cervical cancer, researchers have said. Half of women with cervical cancer in a study group of 371 had not had a smear test in the three years before diagnosis, experts at the department of preventive and social medicine at the University of Otago, New Zealand, said in the journal BJOG.



Scientists find key to kinder cancer drugs-News-UK-Science-TimesOnline