Repair with fatal side effects: The healing process after a brain injury can contribute to the formation of a tumor, according to a study. In doing so, “tumor mother cells” are activated to replace the lost tissue. Due to their mutations, however, they no longer stop dividing and thus form a glioblastoma – the most common and hardly treatable form of cancer in the brain. The findings could now lead to the development of new treatment options for glioblastoma patients, say the researchers.
“You have a tumor in your brain that we can hardly do anything about – you have little life left”. These are the terrible facts that medical professionals have to confront patients who have had a brain known as a glioblastoma. Surgical removal of the tumor tissue can save a little time, as cancer cells usually remain, which lead to rapid regrowth. Other forms of treatment can hardly stop the disease from progressing. The average patient survival time after diagnosis is therefore only 15 months.
As with other types of cancer, the tumor tissue of the glioblastoma also emerges from mutated cells whose normal division activity is disturbed so that they proliferate. Canadian researchers have now devoted a study to the special characteristics of glioblastoma cancer cells. “The goal is to find a way to specifically kill glioblastoma cells. To do this, we need to better understand the molecular nature of these cells, ”says co-author Gary Bader from the University of Toronto. To this end, the team collected cells from the tumors of 26 patients and multiplied them in the laboratory in order to obtain sufficient test material. The scientists then subjected thousands of individual cancer cells to RNA sequencing in order to determine in detail which genes are active in them.
Immune signatures are emerging
As they report, they identified the molecular signatures of an inflammatory or healing process in some of the glioblastoma cells: genes that react to inflammation markers such as interferon and TNF alpha are upregulated, which indicates wound healing processes. As the researchers explain, this suggests that some glioblastomas arise in connection with the repair processes that occur after tissue damage, such as those caused by tremors, strokes, or some infections. Cells are stimulated to replace lost tissue.
However, if they are glioblastoma precursor cells, the system can derail, the results suggest: As soon as a mutated cell intervenes in wound healing, it can no longer stop reproducing because its normal control functions are disturbed. “Glioblastoma can be thought of as a wound that never stops healing,” explains co-author Peter Dirks from the University of Toronto. “These new indications could now lead to completely new treatment approaches that focus on the effects of injuries and inflammatory reactions,” says the scientist.
Hope for hopeless cases
The scientists also found specific gradients in the condition of the cancer cells in the patients’ tumors: According to this, some are more influenced by tissue healing processes than others. The relative ratio of the two states of the cancer cells is patient-specific. The researchers also found evidence that the two conditions show different responses, which leads to indications of treatment options.
“We are now looking for drugs that are effective at different points on this gradient,” says co-author Pugh Trevor of the Princess Margaret Cancer Center in Toronto. “There is a real opportunity for precision medicine – we can analyze patients’ tumors at the single-cell level and develop a drug cocktail that can turn off more than one cancer cell version at the same time,” the scientist hopes.
Source: University of Toronto, Article: Nature Cancer, doi: 10.1038 / s43018-020-00154-9