Scientists from the German Cancer Consortium (German acronym: DKTK) at the Charité - University Hospital of Berlin have succeeded in describing the effects of characteristic gene mutations at the individual cells level. This experimental approach could open up new colorectal cancer treatment options.
Until now, it was assumed that the changes in the KRAS and BRAF genes led to similar growth signals in all cancer cells. However, this assumption seems to be wrong, as the research team around Markus Morkel and Nils Blüthgen from the German Cancer Consortium (DKTK) at Charité Berlin have now investigated in detail.
"We were surprised that mutations in the KRAS gene only triggered a cell response in part of the cancer cells in colorectal cancer, but not in others. The difference seems to lie in cell differentiation, i.e. in the cancer cell's efforts to mature into a certain cell type. The mutated BRAF gene, on the other hand, activated growth signals in all cell states," said Morkel summarising the main discovery of the study.
For tumors with altered KRAS, there is still no targeted therapy option available. The new study results are therefore very important for optimizing the treatment of colorectal cancer in the long term. In colorectal cancer with mutated KRAS, only some of the cells transmit altered growth signals, so the tumor remains very heterogeneous. That makes it very difficult to access when required by therapy.
"Our results suggest that therapies will have to be combined in the future in order to first synchronize the colon cancer cells, i.e. to bring them into a uniform state. In addition to its basic scientific importance, this discovery could also be clinically relevant, as our investigations can help to develop future targeted combination therapies," said Blüthgen explaining the importance of the study data.
These results were made possible by single-cell analysis. In addition, Morkel and his team used organoid technology. What is special about this is that cancer tissue cells obtained from surgical material grow into three-dimensional structures in the laboratory. In addition, computer simulations were used to understand where signal processing can be blocked by the cell itself.
According to the study results, the cancer cell is able to switch on or off the information chain for uncontrolled cell division at certain points. This also explains the frequent observation that certain signaling pathways within an intestinal tumor are not active in all cancer cells, but only in some of them - and this, in turn, has an effect on the treatability of the tumors.