Enzyme new potential target in treating blood cancer

By stopping the production of a specific enzyme, ICMT, researchers were able to alleviate disease symptoms in mice with blood cancer.

In many forms of cancer, the growth of tumors and their ability to spread are stimulated by a mutated gene that codes for a so-called RAS protein. This has led to intensive research into how to block the activity of these proteins.

“RAS proteins exist in all cells, anchored to the inside of the cell membrane, where they regulate cell growth and cell division. The enzyme we are studying helps RAS proteins get anchored to the cell membrane. By blocking this enzyme, we were able to inhibit the binding of RAS proteins to cell membranes and greatly improve the disease symptoms in mice with blood cancer,” says Associate Professor Martin Bergö, who directs research at the Wallberg? Laboratory at the Sahlgrenska Academy.

The research team has developed a genetically modified mouse that produces a mutated and constantly active RAS protein in its bone marrow, where new blood cells are generated. These mice develop a form of leukemia that is similar to a number of forms of blood cancer in humans. The pathogenic bone marrow cells divide uncontrollably, and the normal control of cell growth cannot turn them off. In these mice, the production of the enzyme called ICMT can also be stopped.

“When we inhibited the production of the enzyme, the development of blood cancer declined, and the uncontrolled growth of bone marrow cells was blocked. Another discovery was that normal bone marrow cells were not significantly affected by the ICMT enzyme. The means that future drugs for inhibiting ICMT could specifically target the pathogenic cells and leave normal cells intact. A drub that blocks this enzyme could be an effective future cancer treatment,” says Martin Bergö.

The research team also demonstrated that mice with an aggressive form of lung cancer lived longer and developed considerably smaller tumors when the ICMT enzyme was blocked. But even though the study strongly indicates that ICMT can be an effective target for cancer treatment, the findings now need to be corroborated by other mice with blood cancer and lung cancer, and drugs to inhibit the enzyme need to be produced and tested.

Journal: Blood
Title of article: Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease

Authors: Annika M. Wahlstrom, Briony A. Cutts, Meng Liu, Annika Lindskog, Christin Karlsson, Anna-Karin M. Sjogren, Karin M.E. Andersson, Stephen G. Young, and Martin O. Bergö

For more information please contact:
Associate Professor Martin Bergö,
phone: +46 (0)31-342 78 58; cell phone: +46 (0)733-12 22 24;
e-mail: martin.bergo@wlab.gu.se