Potential new target for cancer treatment

In many forms of cancer the growth of tumors and their capacity to spread is stimulated by a number of CAAX proteins. This has led to intensive research into how to block the activity of these proteins.

“The enzyme we are studying develops CAAX proteins so that they will take on the properties that stimulate cancer growth. By blocking this enzyme, we may be able to reduce the modification of CAAX proteins in a new cancer model in mice,” says Associate Professor Martin Bergö, who directs this research at the Wallenberg Laboratory, Sahlgrenska Academy.

The research team uses a genetically modified mouse that produces a muted and constantly active CAAX protein. This is a new model for an extremely aggressive lung cancer and a mild form of blood cancer. In these mice, the production of an enzyme called GGTas1 can also be stopped.

“When we inhibited the production of the enzyme, tumor development decreased dramatically. The mice survived considerably longer, and all signs of blood cancer disappeared. A drug that blocks this enzyme can be an effective future cancer treatment,” says Martin Bergö.

The findings strongly indicate that the enzyme GGTas1 is a promising target for cancer treatment. At the cell level, inhibition of the enzyme resulted in blocked cell growth and decreased cell mobility.

“Another interesting discovery in this study was that many types of cells appear to be able to survive without the enzyme. This is important from the point of view of toxicology, since you want a drug to attack only the cancer cells and not normal cells and tissues,” says Martin Bergö.

The research team is now pursuing the question of whether GGTas1 can also be an effective target for treating other types of cancer. They will also be ensuring that inhibiting this enzyme does not damage other cell types and tissues.

For more information, please contact: Associate Professor Martin Bergö, phone: +46(0)31-342 78 58; e-mail: martin.bergo@wlab.gu.se Journal: Journal of Clinical Investigation Title of article: GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer Authors: Anna-Karin M. Sjögren, Karin M.E. Andersson, Meng Liu, Briony A. Cutts, Christin Karlsson, Annika M. Wahlström, Martin Dalin, Carolyn Weinbaum, Patrick J. Casey, Andrej Tarkowski, Birgitta Swolin, Stephen G. Young, Martin O. Bergö