Activities of Laboratory oncology translation research group
Laboratory oncology translational research group FNUSA-ICRC (LOTR) focuses primarily on pediatric oncology and its goal is to bring new knowledge in the field of tumor biology into practice. The team led by prof. RNDr. Renata Veselska, Ph.D., M.Sc. and works closely with clinical oncologists and pathologists so that laboratory research can be used as soon as possible to create new ways to treat patients. “We focus mainly on detailed molecular characterization of a particular tumor, which is crucial in terms of identifying targets for so-called precision therapy, and we also deal with tumor stem cells, which play a key role in the mechanisms of tumorigenesis,” said prof. Veselska. LOTR has several publications in prestigious magazines, some of which we will take a closer look at.
Very important knowledge about the biological properties of rhabdomyosarcoma, a tumor that typically affects children´s muscle tissue, was published by a team of authors from the Laboratory of Tumor Biology MU and the LOTR research team led by RNDr. Jan Skoda, Ph.D. and prof. Veselska in the magazine Cancers, which ranks among the 25% of the best in the Oncology category. The authors described a new approach to the study of the molecular characteristics of highly aggressive rhabdomyosarcoma cells, ie the so-called tumor stem cells mentioned above. These cells are often resistant to anti-tumor therapy and are responsible for tumor regrowth and metastasis. Under laboratory conditions, tumor stem cells are characterized in that they are the only one of all cells in the tumor mass capable of initiating tumor formation and growth. This was used by the authors of a published study and showed that during the repeated injection of rhabdomyosarcoma cells into mice, the proportion of tumor stem cells increases in individual samples. They were the first to provide evidence that rhabdomyosarcoma tumor stem cells occur in a highly plastic state, showing signs of epithelial and mesenchymal cells, which could explain their ability to respond to changes in the microenvironment or to resist anti-tumor therapy.
The article can be found here: https://doi.org/10.3390/cancers12010196
Another publication, published in the international journal Cells, showed a very unusual and as yet unknown localization of the NANOG protein within the cell. This protein is known as a transcription factor important, for example, for the proper function of stem cells, and its presence is therefore typical of the cell nucleus. Authors led by dr. Skoda and prof. Veselska described an unusual localization of the NANOG protein within the centrosome, a structure that is significantly involved in many physiological processes in the cell, including cell division. The results of the study clearly showed that NANOG is found in the centrosomes of cells of various origins, from embryonic stem cells and fibroblasts to many types of tumor cells. “It is also completely new to know that the presence of NANOG protein within the centrosome changes in individual phases of the cell cycle,” added Mgr. Erika Mikulenkova, the first author of the article, who points out the possible, as yet undescribed role of the NANOG protein in the process of centrosome duplication, which is very important in terms of understanding the functions of the transcription factor NANOG in the cell.
The article can be found here: https://doi.org/10.3390/cells9030692
The development of resistance in cancer is one of the most common reasons for failure of their treatment and relapse. A review article has been published in the International Journal of Molecular Sciences on the problem of the use of low molecular weight tyrosine kinase inhibitors in anticancer therapy. Under the leadership of prof. Veselska, the authors of the work focused on a summary of existing knowledge about the interactions of tyrosine kinase inhibitors with membrane transporters – “pumps”, which are able to remove drugs from tumor cells. The article provided a new perspective on the potential clinical use of tyrosine kinase inhibitors, some of which could be unconventionally used to block the activity of membrane transporters responsible for resistance. “Based on the synthesis of previous studies, we also outlined various treatment strategies that could lead to overcoming drug resistance and improve the success of cancer treatment by appropriate combination of a tyrosine kinase inhibitor with conventional cytostatics or other targeted drugs,” described Mgr. Maria Krchniakova, the first author of this work.
The article can be found here: https://doi.org/10.3390/ijms21093157