Precision attack on cancer cells

2009/6/10

Every person is an individual whose body reacts in its own way — and scientists are now beginning to exploit such differences in the areas of diagnostics and treatment. Initial results on the path to customized therapies are encouraging: Among other things, scientists have succeeded in detecting genetic mutations in cancer cells.

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The analysis of the tumor DNA makes it possible to determine which type of therapy is most effective for patients

The consequences of first discovering colon cancer in its later stages are grave. If the cancer is identified at an early stage, however, it can be cured relatively easily with an operation. Still, if the cancer has metastasized and moved into neighboring tissue, the chances of patient survival become very slim, even if chemotherapy is used. A new type of test now provides information early on with regard to the type of colon tumor present, enabling doctors to battle the cancer with specialized drugs such as Erbitux® (cetuximab) from Merck. The test marks an important further milestone on the path to customized cancer treatments.

Effective treatment here requires an understanding of certain aspects of uncontrolled cell reproduction. The growth of each cell in a human body is regulated by a complex network of internal messenger substances and molecular switches. A key component of the signal chain here is the EGF receptor, a protein molecule that projects from the cell and is activated by epidermal growth factors (EGF). The EGF receptor acts as a catalyst for a chemical reaction inside the cell. It thus serves to activate other molecules, transmitting the signal so that the cell starts to divide.

Aberrant growth

Practically all colon cancer cells have EGF receptors that continually stimulate cell growth. It’s therefore logical that various treatment approaches have endeavored to find a way to shut down the EGF receptors in the cells. For several years now, this goal has been achieved with a special antibody known as Erbitux®, which attaches itself from the outside to the EGF receptor. Erbitux® has been approved for colon cancer treatments in Europe since 2004. The drug improves a patient’s chance of survival and also has significantly fewer side effects than chemotherapy, which is not as targeted in its effect.

From the very beginning and step by step, the development of Erbitux® was geared toward establishing customized cancer treatments. The first step involves finding the target — in other words determining where the drug has its effect, what exactly it is “aimed” at, and how this can be used. “We began addressing this issue very early on,” recalls Dr. Oliver Kisker, Head of Global Clinical Development within the Merck Oncology Unit. “First we studied tumor cells in patients to determine whether or not they even contained EGF receptors.” That didn’t satisfy the scientists, so their next goal was to identify those patients for whom the probability was high that they would respond positively to Erbitux®. The key question here was: Is it possible to predict a patient’s reaction to the drug?