Personalized medicine: fighting cancer with precision medicine

Cancer — it is still one of the biggest challenges facing medical science. But never before have researchers been able to draw on such a comprehensive body of knowledge about the most minute details of a disease that frightens people like practically no other. This is because cancer is first and foremost a disease of the genetic material of certain cells, and the pathological process is a consequence of that.

The entire human genome was decoded less than 15 years ago. New analytical technologies were developed specifically for this purpose, and they have already been bearing fruit for a long time. Increasingly, special tests can be used to adapt treatments precisely to the condition of the individual patient. This vision is called “personalized medicine,” and among clinicians, it is also known as “targeted therapy using biomarkers.”    

Professor Thomas Kirchner, director of the Institute of Pathology at the Ludwig-Maximilians University of Munich, is an expert in the analysis of these special, individual characteristics that vary among patients: “Biomarkers are indicators that give us information about the type and progress of a disease. There are two types, the prognostic and the predictive biomarkers. The prognostic biomarkers allow us to estimate the expected course of a disease. The predictive biomarkers, on the other hand, can tell us whether we can expect a specific drug to have an effect in this or that particular patient.” 

The same thing applies to colorectal cancer. Worldwide, about 1.2 million people develop this disease every year and it is the cause of death for an estimated 608,000 people per year. In Europe alone, there are 436,000 new cases annually and 212,000 deaths from this cancer. The prognosis is especially poor if the tumor was identified at a late stage and has already formed metastases. In addition to regular chemotherapy, treatment with new types of biotechnological pharmaceuticals are possible in cases such as this. 

One of these pharmaceutical products is Erbitux®, a “monoclonal antibody”. This specially adapted protein molecule locates a specific receptor on somatic cells that regulates the growth of tumor cells in many intestinal-cancer patients. When it binds to that receptor, the growth of these tumor cells is inhibited. Normally, the receptor responds to the body’s own epidermal growth factor (EGF), and the cancer cells react to this by quickly multiplying uncontrollably. Erbitux® switches this “stimulator” off and can thereby greatly inhibit the progress of the disease.

This is not possible for all patients, however, as Professor Kirchner explains: “The signal of the EGF receptor is transmitted into the cell through several additional stages.” This is called a signal transduction pathway — it transmits the growth signal to the nucleus of the tumor cell that initiates cell division. One stage along this path is the RAS proteins. And the genes that provide the template according to which these proteins are formed in the patient’s body can likewise be changed by mutations: “In this case, Erbitux® cannot have its intended effect,” says the specialist. “As a result of the changed RAS genes, the signal path remains switched on without any interruption.”    

Here, the pathologist now brings a specially developed predictive biomarker into the picture. In addition to the conventional examinations of tumor tissue, he can use this biomarker to predict the expected effect of Erbitux® — and the treating physicians can then prescribe it to only those specific patients who can really benefit from the therapy. The terms of approval of the drug in Europe were thus modified after studies had shown corresponding results: it is to be administered solely to patients with the “wild types” of RAS. “The term ‘wild type’ sounds unusual,” says Professor Kirchner, “but it comes from the geneticists who did their basic research on the fruit fly, genus Drosophila. The normal gene in any particular case is the one that occurs in a wild, unmodified fly, and the mutations occur in genetically modified flies.” 

With the combination of the biomarker test and the antibody therapy, patients can expect that their treatment will actually have an effect. In this way, personalized medicine is overcoming a challenge that preoccupied doctors for a long time. In the past, all the patients suffering from an illness were given a drug, and the drug selected for itself the patients it would work on, so to speak. In the future, as biomarkers become increasingly diverse and the information they reveal grows more specific, they will be able to eliminate this uncertainty. 

Research on medicines and their ideal range of uses thus continues even after these medicines are launched on the market. New insights allow a company such as Merck KGaA, Darmstadt, Germany to adapt the use of its products precisely to the needs of patients. Currently, researchers are hard at work on a further crucial improvement that applies specifically to the Erbitux® therapy: in the future, a simple blood-based test is expected to replace tumor tissue samples in RAS biomarker testing. The company has been pursuing this solution in cooperation with the company Sysmex Inostics, a specialist in this field.

Progress of this kind also benefits the treating physicians — ultimately to the benefit of patients once again. “In the final analysis, an exact adaptation of the therapy means that it can provide clear evidence of its benefit. Then doctors can realistically expect a positive outcome. And for the health care system, it means that the use of antibody therapy is justified,” says Kirchner. In his laboratory, he is already conducting a whole series of biomarker tests. One can discern a clear trend of efforts to advance personalized medicine in many different areas. Accordingly, Kirchner is devoting considerable effort to the issue of quality assurance for biomarker diagnostics: 70 institutes in Germany have already acquired a certification for the biomarker analysis in the case of colorectal cancer. The trend toward personalized medicine is unmistakable.