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The Warsaw Voice » The Polish Science Voice » December 21, 2012
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Targeting Breast cancer
December 21, 2012   
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Breast cancer is the most common type of malignant cancer in women and a leading cause of cancer-related deaths. Many of those attacked by breast cancer die because the tumor tends to metastasize to other, distant areas in the body. Polish researchers are now studying ways to prevent breast cancer and how to predict where it is likely to attack again.

Researchers dealing with breast cancer must first understand the exact mechanism of metastasis and discover the markers that will tell them more about it. This is a precondition for the emergence of better treatment, less aggressive for the patient and tailored to the individual needs of each patient.

This is the aim behind the “Analysis of selected molecular invasiveness and metastasis factors in breast cancer patients” project managed by Anna Żaczek, Ph.D., a biotechnologist at the Medical University of Gdańsk. The results of the analysis are expected to help the team develop a diagnostic method that will be invaluable in clinical practice. The National Center for Research and Development has allocated zl.850,000 for the project under its Lider (Leader) program for research staff development.

“Our main goal is the most effective treatment of patients in the clinic,” says Żaczek. “And this depends on better understanding of the molecular factors that control cancer invasion and metastasis. Our analysis will help identify new biological markers in breast cancer, which are still not known to researchers despite the enormous body of research work done.” Markers, such as those for HER2 protein levels, help physicians classify patients into risk groups and select the right type of treatment for them.

Women are still dying from breast cancer because there is an insufficient number of markers allowing for more individualized treatment. And factors such as tumor size or the presence of metastases in the lymph nodes do not provide enough information to select the best treatment options.

The research being conducted by Żaczek can therefore give doctors an important tool, a method that will make it possible to identify new prognostic factors pointing to the chances of survival and predicting the effectiveness of a particular type of treatment.

The new standard of care would allow for more accurate prediction of the course of the disease. Doctors would be able to use the new markers to more precisely determine which drugs and medical procedures would work best for their patients. If, from among all patients with breast cancer, doctors can single out those in whom the disease is likely to take a less aggressive course, it will be possible to spare these patients unnecessary chemotherapy and its side effects. This will help not only improve their quality of life, but also reduce the costs associated with the cancer treatment involved.

“Unfortunately, we still do not fully understand the mechanisms of the individual stages of how cancer spreads,” says Żaczek. Despite the enormous body of breast cancer research there is still a lack of information about molecular factors underlying the process of invasion and metastasis. This explains why there is so much demand for this knowledge. One still unanswered question is why some tumors metastasize quickly, while others take years to do so. Why do dormant cancer cells wake up? And are all the disseminated cells that get into the blood bound to metastasize? If researchers find an answer to these questions, perhaps this may help doctors better diagnose and treat patients, and consequently save thousands of women.

As part of the project, Żaczek intends to conduct studies of molecular changes occurring in cancer cells at the gene and protein level. These changes allow the cells to multiply locally and then detach from the primary tumor, invade the neighboring tissue and finally move into the bloodstream, which carries them to distant areas of the body, allowing the formation of metastases.

“The very presence of cancer cells in the blood is a bad sign for patients—it is associated with shorter life expectancy and resistance to treatment,” says Żaczek. In addition, the currently used methods for marking these cells are still imperfect and their characteristics are poorly understood.

Aleksandra Markiewicz, a member of Żaczek’s team and one of the winners of the InnoDoktorant (Innovative Doctoral Student) scholarship project, says, “It is molecular changes that allow primary tumor cells to transform into an invasive type that determines the spreading of the cells into the bloodstream and the formation of metastases in a remote area of the body.”

Żaczek’s team is working on a method to enable the identification and characterizing of cancer cells detached from the tumor and circulating in the bloodstream that could trigger the formation of metastases. The researchers are working to examine what molecular characteristics of tumor cells are associated with their activation in the blood, how the malignancy of these cells increases and how they colonize new locations in the body. The analysis of the cells will make it possible to identify, within the general population of breast cancer patients, particularly aggressive cases capable of forming distant metastases.

“The number of cancer cells circulating in the blood may be very small, so we need to develop sensitive and specific methods for detecting and isolating them,” says Markiewicz. The techniques currently in use are only capable of detecting a certain percentage of circulating cells.

According to Żaczek, the developed method makes it possible to identify cancer cells without using big, expensive equipment, but only on the basis of simple magnetic selection. Studying those circulating cells that have been detached from the primary tumor and have entered the blood is like a “liquid biopsy,” Żaczek says. It is a non-invasive tool that makes it possible to gain an insight into the process of the formation of cancer, assess if the tumor is spreading cells, if these cells are aggressive or not, and whether or not the patient is responding to treatment. The cell count changes during the treatment: the number of cells falls when treatment is effective, and does not change when the patient is resistant to treatment.

“A fascinating aspect of the research is that it combines the latest discoveries in the molecular biology of cancer with clinical practice and may have a direct impact on the development of more effective diagnostic and therapeutic methods to treat breast cancer,” says Żaczek. “Knowledge resulting from the analysis of disseminated cancer cells will be useful for both physicians and patients. Our method may therefore be an important tool in the hands of physicians, assisting them in an individual approach to treating breast cancer patients, and in more accurate monitoring of the disease. It will also allow them to predict the effectiveness of treatment.”

The researchers have found a niche in which they have no competition. In Poland, no other research center deals with such research. Analysis of disseminated cancer cells is a rapidly changing and at the same time difficult area. It requires sensitive methods for identifying one cancer cell per 1 million normal blood cells on average. Żaczek’s team is preparing to have their method patented, in what is a prelude to future collaboration with industry.

It is worth noting that the project is being carried out by an interdisciplinary team of young researchers—three molecular biologists, two pathologists and a coordinator responsible for the collection of clinical material. They are supported by experts with years of experience in clinical oncology, pathology and biomedical statistics—including professionals heading the Department of Oncology and Radiotherapy, the Department of Oncological Surgery and the Department of Pathomorphology at the Medical University of Gdańsk.

For more than 10 years, the research team has been working with a group of clinicians from the Medical University of Gdańsk’s Department Oncology and Radiotherapy, headed by Prof. Jacek Jassem.

This collaboration of researchers and practitioners continues to invite discussion and prompts new questions. The project originated with a question about being able to predict the course of disease in patients with early breast cancer. The project will end in the second half of 2013.

Żaczek has demonstrated that together with her team she is prepared to undertake research work on a project that can be applied in practice. A team of experts from the National Center for Research and Development gave high ratings to the professional level and innovativeness of the project, the project management concept and the prospects of putting its results to a commercial use.
Karolina Olszewska

Polish Biotech Drug Against Breast Cancer

In another research project aiming to help patients with breast cancer, Polish researchers at the Medical University of ŁódĽ, working in collaboration with experts from biotechnology company Mabion, have developed an innovative biotech drug against breast cancer—in a project called “the development of a humanized monoclonal antibody that binds to the HER2 receptor and can be used in the treatment of breast cancer.”

Unlike standard chemotherapy, biotech drugs are far less harmful to the patient, the researchers say. However, most biotech drugs available internationally carry a steep price tag and many patients in Poland cannot afford them. The Polish drug is expected to be less expensive.

The research team, led by Prof. Tadeusz Pietrucha, who heads the Department of Medical Biotechnology at the Medical University of ŁódĽ, began working on the drug in 2008. At the moment, the project is being developed and implemented in a biotechnology company and is at the clinical trial stage.
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