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. 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 reference:
Wahlstrom et al. Inactivating Icmt ameliorates K-RAS-induced
myeloproliferative disease. Blood, 2008; 112 (4): 1357 DOI:
10.1182/blood-2007-06-094060