Scientists from Far Eastern Federal University (FEFU) in cooperation with colleagues from Blokhin Russian Cancer Research Center (Moscow), Switzerland, and Sweden for the first time studied proteins, which constitute WNT signaling pathway of the cancer stem cells of glioblastoma multiforme (GBM CD133+ CSCs), one of the most aggressive brain tumors. Researchers revealed a number of proteins, which are potential targets to attack during complex antitumor therapy. A related article was published in Oncology Reports.
Glioblastoma multiforme (GBM) is one of the most aggressive brain tumors that is extremely resistant to therapy. On average, patients with such diagnosis live for 15 months. Only 27% of patients live more than two years following the diagnosis. According to scientists, tumor resistance to treatment is associated with cancer stem cells, and, in particular, with the activation of WNT signaling pathways in them.
WNT signaling pathways in human cells are responsible for a number of essential functions, including cell proliferation, i.e. their reproduction, and the ability to differentiate into other types of cells. Unfortunately, they can contribute to the proliferation of cancer cells.
"The behavior of the stem cells of glioblastoma multiforme is an urgent spot calling for research in modern medicine. Irradiation, cytostatics, and contemporary targeted chemotherapy are almost ineffective against cancer stem cells. Our idea is to use radiation simultaneously with drugs that suppress DNA retrieval process in cancer cells, followed by aggressive chemotherapy, one of the strategic objectives of which is to attack cancer stem cells." said Igor Bryukhovetskiy, the author of the research idea, the Director of the Department of Fundamental Medicine in the FEFU School of Biomedicine.
The scientist emphasized that he and his colleagues for the first time have managed to study proteins that form the WNT signaling pathway and directly interact with its components in human CD133 + stem cells of glioblastoma multiforme. The researchers found out that the set of proteins (proteome) in glioblastoma stem cells differs fundamentally from the one in other types of tumor cells. Scientists have also recognized other potential targets, the massive suppression of which can lead to a significant improvement of complex antitumor therapy outcome. These important results need further refinement during new in-depth research.
How to affect the glioblastoma cancer stem cells is a conundrum far from a trivial. To crack one has engaged the world best laboratories.
"In our research, we proceed from the fact we have proved previously: cancer stem cells execute their full potential when building up a bloodstream of a tumor, significantly accelerating its growth rate. Suppression of WNT-signaling proteins will allow increasing the effectiveness of anti-angiogenic therapy, i.e. treatment directed against the formation of new microvessels based on the vascular network already existing in the tissue. Such therapy is an integral part of the modern protocol for the comprehensive treatment of glioblastoma. The results of our studies can be brought into clinical practice in the near future." summed up Igor Bryukhovetsky.
Original article: Proteins of the Wnt signaling pathway as targets for the regulation of CD133+ cancer stem cells in glioblastoma, DOI 10.3892/or.2019.7043, https:/