Enzyme New Potential Target in Treating Blood Cancer

A discovery by a research team with the Sahlgrenska Academy at Gothenburg University in Sweden may lead to new treatments for blood cancer and other diseases.

A research team with the Sahlgrenska Academy at Gothenburg University in Sweden has made a discovery that may lead to new treatments for blood cancer and other diseases. The research team stopped the production of a specific enzyme, ICMT which alleviated 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. A genetically modified mouse has been developed. The mouse produces a mutated and constantly active RAS protein in its bone marrow, where new blood cells are generated. The modified 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. In addition, the research team demonstrated that mice with an aggressive form of lung cancer lived longer and developed considerably smaller tumors when the ICMT enzyme was blocked. 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.