Munich

Not content with genomes and proteomes, biologists have added another ‘-ome’ to their lexicon: the degradome. Its proponents say that it signals a fresh approach to cancer research. And the European Commission seems to agree — on 15 June it awarded one of the largest-ever grants for life-sciences to a four-year project based on the concept.

The degradome encompasses all of the enzymes in the body that degrade proteins. There are about 560 such enzymes, called proteases, in humans. Many of them modify the environment of human tissues and contain their growth — making sure a liver stays liver-shaped, for example.

The range and levels of proteases expressed by a tissue change dramatically if it becomes cancerous. For example, normal tissue cells are fixed in position by a matrix. But cancer cells seek to break this down using certain proteases, so that they can escape into the blood stream and establish themselves in different tissues. Other proteases are marshalled to help build the blood vessels needed to feed growing tumours.

But therapeutic approaches based on disrupting such protease activity have so far been unsuccessful in clinical trials. Dylan Edwards, a cancer biochemist at the University of East Anglia in Norwich, UK, and coordinator of the €10.4-million (US$12.6-million) project, says that this is because the drugs tried have been designed to inhibit as many proteases as possible.

“Dogma has insisted that protease action must be blocked in as broad a manner as possible in cancer,” says Edwards. “But we now know that the web of proteases is complex. Some of them inhibit, rather than facilitate, cancer growth.” So researchers in the European project plan to investigate the biology of proteases and then design specific inhibitors to block them individually.

Involving 41 scientists from 13 countries, the project will cut across many different disciplines. It will depend initially on two mouse models — for breast and prostate cancer — later expanding to include colorectal and skin cancers. Biologists will study the expression of proteases to untangle which protease does what in normal and diseased tissues. The chemists in the team will work on developing highly selective inhibitors for diagnostics and therapeutics.

→ http://www.cancerdegradome.org