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Genetic analysis determines treatment

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Clarify mechanisms and develop therapies that will become the standard worldwide. That is what the Department of Internal Oncology of Erasmus MC Cancer Institute did for several types of cancer. An interview with department head Stefan Sleijfer.

“The concept of tailored therapy, or personalized medicine, is used so much nowadays that we almost forget that it was very different not so long ago,” says Sleijfer, professor of Medical Oncology. “Roughly thirty years ago all women with breast cancer received hormonal therapy because research showed that a small number of patients responded well to this. It was discovered later that the therapy works through connective spots,  strogen receptors, which can be found on the outside of the tumor cell. But far from all breast cancer cells have these receptors. A woman with this type of cancer will not be helped by hormonal therapy. Nowadays hormonal therapy is only used on women with breast cancer where the receptor is present. The importance of fine-tuning the treatment is increasingly acknowledged and increasingly possible.”

Profile

At the same time ‘tailored therapy’ does not mean that the treatment will be different for every individual patient, according to Sleijfer. “That is just not possible on a practical level. What does happen more and more is that doctors differentiate between various groups of patients who seemingly have the same type of cancer. Are there similarities in certain characteristics, such as the genetic characteristics of the tumor cells? A certain genetic profile of the tumor cells leads to a specific treatment.”

Thanks to technical developments, scientists are increasingly able to separate tumors into subclasses. Sleijfer: “This used to only be possible based on observations with the naked eye. Then methods were developed to differentiate between cells under a microscope using stains. Nowadays we are able to map the genetic profile of tumors. Especially this genetic analysis has accelerated personalized medicine. We can now determine mutations in the DNA, changes to the genetic information of the tumor cell, which provide clues to the most efficient treatment.”

Classic or new

Tailored therapy involves choices: which patient will benefit from a certain treatment and which will not? Sleijfer gives an example: “A melanoma is a type of skin cancer which is based on the pigment cells. Those cancer cells can metathesize to other organs. 50% of patients with melanoma show a mutation (in the BRAF-gene), making them more susceptible to treatment with a new drug. Patients with tumors that do not show the same mutation, do not profit from that new drug. They receive classic chemotherapy. That same BRAF-mutation is also seen in a certain type of intestinal cancer. We are now studying whether this treatment works in patients with intestinal cancer and this BRAF-mutation.” In the near future drugs will more and more only be given to patients who have a significant chance that the drug will work. And at the time of day and in a dose which is expected to give the best result for that patient. Sleijfer: “Therefore tailored therapy benefits the costst effectiveness of the treatment. That is important, because the number of people with cancer is growing, mainly due to the aging population. If we wish to provide good care to  everyone in the future, cost control is inevitable.”

Better survival time

Will the improved treatments lead to cancer being considered a chronic disease at a certain point? Sleijfer: “I’m very cautious with statements like that. Certainly enormous strides have been taken for certain types of cancer, such as Gastro-Intestinal Stromal tumors (GIST). Professor Jaap Verweij has done a lot of work in this area. GIST is a rare type of cancer where tumors develop in the supportive tissue around the organs, often the stomach or the small intestine. Those tumors have a mutation in the DNA, making them extra sensitive to a certain drug (Imatinib). Thanks to this treatment the average survival time of patients has gone up from nine months to approximately five years. And 10 to 15% of these patients benefits from Imatinib for over ten years.” But GIST is not representative for all types of cancer. Sleijfer: “GIST are relatively ‘dumb’ tumors. They often only have one motor driving their cell division. If you can disable this motor with Imatinib for instance this immediately has huge consequences. Most other tumors are not so easy to deal with. They are built up from many different tumor cells with very varied characteristics. A tumor is often a collection of tumor cells which have different motors driving the cell division. One drug can ill a part of the cancer cells, but other cells survive: they have mechanisms which allow them to escape and which allows the tumor to spread, in spite of a treatment that was initially successful.”

Adapted

Sleijfer’s ambition? “A cancer treatment like we apply to HIV. There the therapy is tuned to the mutations shown by the virus particles. The therapy is adapted to each new mutation. A combination therapy tackling various mutations simultaneously is the most effective. But there is an important difference.  An HIV-virus particle is totally foreign to the human body and genetically much simpler than a tumor cell. A cancer cell stems from a body cell and therefore has many characteristics inherent to the body. That makes it a lot harder to find a therapy that only targets the tumor cell.”

Progress

The Department of Internal Oncology has made a significant contribution to the progress in patient treatment. Sleijfer: “For instance in the area of breast cancer, ovarian cancer, GIST, testicular cancer, prostate cancer, soft tissue tumors and esophageal cancer. We have clarified mechanisms and developed therapies which are now the standard worldwide. The same goes for other departments within Erasmus MC which are active in the field of oncology. Take prostate cancer screening and colonic cancer screening for instance, and the treatment of acute myeloid leukemia, multiple myeloma and brain tumors.”

Treat and fight

The field Stefan Sleijfer works in aims at the medicinal treatment of cancer patients. This includes both the actual treatment of the tumor and the fighting of the symptoms. Internal Oncology is working on therapies such as chemotherapy and more tumor-specific methods.