Scientists find out why tumor cells survive chemotherapy

Staff of the TSU Laboratory of Translational Molecular and Cellular Biomedicine are studying the role of innate immunity in the formation of tumor resistance to chemotherapy. The subject of the study is colorectal cancer, which is difficult to treat and is among the three most common cancers worldwide. The data obtained will help to determine the risk of developing resistance to chemotherapy drugs earlier and to choose the optimal treatment strategy.

According to the World Health Organization, colorectal cancer ranks third in malignant neoplasms in men and second in women. Over 10 years (2005–2015), the number of patients increased by 27.9 percent. In 2015, deaths from colon and rectal cancer reached 774,000 worldwide.

The main problem in the treatment of cancer is the malignant cells’ forming resistance to chemotherapy and radiotherapy. The tumor attracts the innate immunity of the person to its side and reprograms the protective cells, macrophages, whose task is to suppress the neoplasm. Instead of fighting it, tumor-associated macrophages help the tumor survive a chemotherapy attack, grow, and metastasize.

- It is necessary to ensure that after the chemotherapy, macrophages really died. Otherwise, you can get the opposite, completely undesirable result - to help the tumor progress, - explains Julia Kzhyshkowska, head of the TSU Laboratory of Translational Molecular and Cellular Biomedicine, professor at Heidelburg University (Germany). The fact is that the macrophages that survive the chemotherapy rearrange the metabolism, and they form resistance to the drugs. As a result, the former defenders create a supportive microenvironment in which tumor cells can survive.

To block this process, scientists are exploring the programming mechanisms of tumor-associated macrophages. Using molecular genetic studies, the laboratory staff identifies patterns that indicate the susceptibility of patients' immunity to cooperate with the tumor. In particular, they determine whether there is a program change in the monocytes from which macrophages differentiate or, conversely, the patient’s immune system is not inclined to collaborate with the neoplasm.

For research they are using the latest methods, including sequencing the next generation. This approach greatly accelerates the examination of genes and is highly sensitive; in particular, it helps to read genes with low expression.

New fundamental data obtained during the research will help clinicians to calculate the risks of an undesirable effect from chemotherapy even before treatment and to choose the most productive treatment strategy.