Quartet of genes helps cancer spread: study

Using drugs to block a set of four genes stops the spread ofonetype of breast cancer in mice, researchers have found.

Metastasis, or the spread of tumour cells that escape into the bloodstream to invade other sites with secondary tumours, is responsible for much of the deadly nature of cancer. Scientists are therefore looking for specific genes behind metastasis.

In Thursday's issue of the journal Nature, researchers in the U.S. and Spain said they could reduce the growth and spread of human breast tumours in mice by targeting proteins made by the four genes using drugs that are already on the market.

"The remarkable thing was that while silencing these genes individually was effective, silencing the quartet nearly completely eliminated tumour growth and spread," study author Dr. Joan Massagu, a Howard Hughes Medical Institute investigator at the Memorial Sloan-Kettering Cancer Center in New York, said in a release.

The previously identified genes, called EREG, MMP-1, MMP-2 and COX-2, carry instructionsfor creatingproteins that help regulate the growth of both theprimary and secondary tumours, Massagu said.

Those proteins hijacka network of blood vessels that then nourish the growth of the tumour, helping cancercells to escape into blood vessels and reach the lungs, where they get stuck and proliferate, he added.

The researchers used microscopic analysis to compare how the blood vessel structure of tumours changed before and after the genes were turned off.

A combination of the anti-inflammatory celecoxib, sold as Celebrex, and the cancer drug cetuximab, sold as Erbitux, worked against two of the four genes when tested together in mice, but each drug did not work well on its own, the researchers found.

Clinical trials on the combined drug approach are planned.

Improvingchemotherapy

In a secondcancer study appearing in the same issue of Nature, researcherslooked atalmost the whole human genome and found 87 different genes that appear to affect how sensitive cancer cells are tochemotherapy drugs.

When the genes were blocked in laboratory tests, lung cancer cells were up to 10,000 times more sensitive to the chemotherapy drug paclitaxel, or Taxol.

The effects were not as dramatic for two other chemotherapy drugs, vinorelbine and gemcitabine.

It's not yet known whether blocking the genes in living animals would have the same effects.

Chemotherapy is a blunt instrument with inconsistent benefits and side-effects such as fatigue, nausea and hair loss, the second study's senior author noted.

"Identifying genes that make chemotherapy drugs more potent at lower doses is a first step toward alleviating these effects in patients," said Michael White, a professor of cell biology at the University of Texas Southwestern Medical Center in Dallas.