Enter the degradome – fine tuning cancer treatments

Brussels, 12 Jul 2004

Taking what is known about proteomes and genomes to another level, EU scientists are exploring new realms of cancer research. With Commission funding, they will study the complex enzymes in the body that degrade proteins as they look towards developing designer therapies.

A new project with the ominous-sounding title 'Cancer-Degradome' was launched last month by the European Commission to study new ways of diagnosing and treating cancer. A team of 41 scientists from 13 countries – together forming the European Cancer Proteases Consortium (EUPC) – will spend the next four years refining their knowledge of the degradome – the enzymes or proteases in the body that degrade proteins.

The human body has around 560 such proteases which make up 1.7% of the human genome. When functioning properly, their job is to contain unwanted tissue growth by 'degrading' other proteins. But the range and levels of proteases expressed by tissue change strikingly if it turns cancerous. Such mutations of the degradome genes have been linked with numerous human diseases. But the project will explore how these genes contribute to the most prolific types of cancers – starting with breast and prostate, then colorectal and skin.

The journal Nature offers an example of how the body reacts when the proteases turn on it: "[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 bloodstream and establish themselves in different tissue." Then other proteases are called upon to help build the blood vessels required to nourish these growing tumours, it continues.

The good and the bad

While some proteases help the body, others work against it. The problem with therapeutic approaches tested until now is they do not distinguish between the proteases. Coordinator of the European project, Dylan Edwards of the University of East Anglia (UK), says the general tactic in fighting cancer has been to block this rogue protease action in as broad a manner as possible. "But we know that the web of proteases is complex. Some of them inhibit, rather than facilitate, cancer growth," he told Nature.

The consortium of research centres behind this Integrated Project – funded with €10.4 million from the 'Life sciences, genomics and biotechnology for health' theme of the EU's Sixth Framework Programme's (FP6) – aim to improve the diagnosis and therapies, so patients will receive much more targeted treatment at an earlier stage.

To do this, a multidisciplinary team will closely study the expression of the proteases to find out which of them perform what job in normal and diseased tissues. Meanwhile, the EUPC's chemists and biochemists will get to work on developing highly selective therapies which will also minimise adverse side-effects. Assisting in this task, the project will also concentrate on improving tumour-imaging techniques, so that cancers can be localised, characterised and treated as early as possible.

The battle against cancer is high on the EU's priority list, especially as Europe's population ages which could lead to up to 250 000 extra cancer cases a year by 2020, placing greater pressure on health systems. Coinciding with the European Week Against Cancer, in October of last year, the Commission announced it would provide a €100 million boost to European cancer research.

DG Research
http://europa.eu.int/comm/dgs/research/i ndex_en.html
Item source: http://europa.eu.int/comm/research/headl ines/index_en.cfm