New tool discovers evolutionary advantages of multiple myeloma cells across different treatments

MADRID, 7 (EUROPE PRESS)

The study, carried out by the Clinical Research Unit for Hematological Tumors of the 12 October University Hospital and the National Cancer Research Center (CNIO) in collaboration with the University Hospital of Würzburg (Germany), demonstrates a new method based on evolutionary methods on multiple myeloma cells. In theory, it is useful to figure out how each population of cells responds to different drugs to cause tumor resistance, so the information provided can help prevent tumors from developing drug resistance.

Researchers remember that all cells of the same cancer are not the same, since they all have genetic errors that turn them into tumor cells, yes, but these errors are not identical.

“In every cancer there are populations of cells with different mutations, and it is important to know them because one of these populations can predominate and make the cancer resistant to treatment. However, research aimed at understanding the properties of each group of cells in the tumor has so far progressed very slowly,” they note.

EVOLUTIONARY COMPETITION WITHIN A TUMOR

The technique used by CNIO researcher Larissa Hertle, called clonal competition analysis, shows in real time how different populations of tumors cope or fail to adapt to each treatment until a certain population dominates others. It is a very visual tool: different populations of cells are marked with different colors, cultured together, and exposed to the different treatments available. After some time, the color of the population is imposed on the crop, whose genetic profile allowed it to resist the drug used.

BEHAVIOR OF DIFFERENT CELL POPULATIONS

Understanding the behavior of different cell populations is especially important in multiple myeloma, a blood cancer that multiplies very often because it becomes resistant to drugs. Multiple myeloma is “very heterogeneous,” explains Hertl, who reminds us that “many genetic changes coexist in the same tumor, and we have to think of it as if there were many tumors.”

“Clonal competition analysis allows us to see how each population of cells in the same myeloma responds to treatment,” he adds. “This is much closer than conventional methods to the heterogeneity of each patient. And we can see in real time how cells develop,” he adds.

THEY STUDYED THE KRAS GENE

Using these tests, they looked at the KRAS gene, which is altered in 20% of patients with multiple myeloma. They confirmed that two specific KRAS mutations confer an adaptive advantage on the cells that carry them, as they multiplied more than unmutated cells in their tests. They also found three specific changes in other genes that benefit tumor cells only in the presence of two common drugs used to treat multiple myeloma. That is, these treatments provided an adaptive advantage.

“When the drugs were applied, all the other cells died, but the ones that had these mutations survived,” explains Hertle. To prevent the tumor from becoming resistant due to this mechanism, the authors suggest taking “breaks” in treatment or even changing treatment when the above-mentioned mutations are detected in patients.