New biological principle and therapeutic goal for cancer treatment

Pioneering research on leukaemia cells can have identified their vulnerable spot. This new knowledge can now be used to produce more effective medicines.

A group of scientists at the University of Bergen and Haukeland University Hospital made a surprising discovery when they stimulated leukaemia cells with the growth hormone GM-CSF. The reaction of the cells surprised everyone and would seem to indicate that scientists in Bergen have uncovered a new biological principle and consequently, a new therapeutic goal.

"We shouted, and expected to get one reply, but what we got was a bellow from an entire football team," says Project Leader Bjørn Tore Gjertsen, who was recently presented in the renowned American periodical Cell.

Cell membranes contain receptors that are stimulated by a number of environmental factors, among them hormones. This starts a chain reaction between proteins that can in cancer cells result in increased production of substances that hamper necrocytosis (cell death) and encourage cancer. A mutation in receptor Flt3 and how this activates the chain reaction has previously been paid a lot of attention. In the tests carried out by Gjertsen and his fellow scientists, it was the GM-CSF receptor that captured their attention. Patients with Flt3 mutation showed an enormous reaction, in proteins that should in principle be normal. This indicates that the attack should be mounted here, if one is to find effective but gentle methods of cancer treatment.

"We have used tests from thirty patients with an acute type of spinal leukaemia. Compared to young people with lymphatic leukaemia, these patients have little chance of recovery. Life expectancy without treatment is about 2-3 months and only 20 percent are cured by chemotherapy. The study results can in principle also be applied to other types of cancer cells, so these results can prove to be of great importance for future cancer sufferers," says Gjertsen.

In this particular research project, Gjertsen has collaborated with colleagues from Stanford University and also several from the research milieu in Bergen, including Randi Hovland and Øystein Bruserud. With support from the cancer association, Bruserud has over the last twelve years, collected an invaluable bank of leukaemia tests. The Americans were contacted because they have developed a quick method for looking at the activation of proteins with the help of an antibody produced by mice.

"We have invaluable profiles that give us a comprehensive picture of what happens inside the cells. In spite of the huge amount of scientific research on cancer during the last ten years, there have been few important clinical results. This is mainly due to the fact that we have turned one stone at a time and studied the building blocks of the cancer cells individually. In system biology we try to look for patterns so that we can get a complete and realistic overall picture," says Gjertsen, "and adds that the use of cells collected from patients, and not static cell lines, can be the only way to get secure results."

The collaboration now continues with unabated strength, searching for energized key cancer proteins that lie under the signal line studied in the Cell article.