German scientists uncover novel cancer target

Research lead

Scientists at the Helmholtz Centre for Infection Research in Braunschweig, the Hannover Medical School and Leibniz-Universität in Hanover have uncovered the chemical mechanism by which a naturally occurring substance, argyrin, destroys tumours.

The basis for this breakthrough was an observation made by Hannover Medical School scientist Nisar Malek while studying the role of a particular cyclin-kinase inhibitor in the development of cancer.

Malek noted that mice in which the breakdown of the kinase inhibitor was suppressed by genetic change have a significantly lower risk of suffering from intestinal cancer.

Malek approached Ronald Frank, a chemist at the Helmholtz Centre for Infection Research, and the two developed a cell-based assay and screened compound libraries to find compounds that prevent the breakdown of the kinase inhibitor.

They found the inhibitor they were looking for subsequently identified as argyrin - in a library of compounds isolated from the soil bacterium Myxobacteria.

The two scientists then joined up with chemist Markus Kalesse from Leibniz-Universität Hannover to develop a synthetic route to produce argyrin and to elucidate its mechanism of action. In the process they have uncovered a completely new mechanism. “Argyrin blocks the molecular machinery of the cell which breakdowns proteins that are no longer required,” says Malek, “And thereby naturally also prevents the breakdown of the kinase inhibitor in question, the lack of which triggers cancer.”

The research team has conducted studies of the effects of argyrin on mice. “When we treat animals with cancer with argyrin the tumour ceases growing, it decreases by up to 50 per cent and it begins to breakdown internally,” notes Malek.

Scarcely any side effects have been noted. Markus Kalesse says, “We are already altering the argyrin molecule in all details and looking to see if it is possible to improve its performance further. Our goal is to submit such an optimised structure for clinical testing in the near future.”