Researchers’ new findings show that inhibiting the EZH2 protein reduces the growth of cancer cells in multiple myeloma, a type of leukemia in which immune cells grow uncontrollably in the bone marrow. According to researchers, the treatment of this disease is very difficult and almost incurable, so it is necessary to identify new therapeutic targets in cancer cells.
The results of a study in mice published in the journal Cell Death & Disease show that this decrease is due to changes in the metabolism of cancer cells and can be used as an indicator to determine whether the patient responds to treatment by inhibiting EZH2. Gives or not used.
“We treated mice with a type of cancer that is related to multiple myeloma in humans and is an EZH2 inhibitor, and showed several signs that the mice being treated for cancer were growing more slowly,” said Helena Jernberg Wicklund, of Uppsala University in Sweden. Compared to treated mice. This provides further evidence of the likelihood of EZH2 as a target for clinical intervention.
The results of the mouse model encouraged researchers to further investigate what makes cells more sensitive to EZH2 inhibition. Human multiple myeloma cells are more heterogeneous than mouse model cells, and they found that some of the multiple human myeloma cells cultured in humans are sensitive. To further study this phenomenon, the researchers used a global analysis of cellular metabolites in combination with an analysis of gene activity. Sensitivity has been associated with changes in specific metabolic pathways in cells.
“In cells that were sensitive to EZH2 inhibition, the movement and rotation pathways of methionine were altered, an effect we did not see in insensitive cells,” Wicklund said. This change is due to the poor regulation of genes involved in methionine movement.
According to the research team, the frequent changes in the metabolites of methionine can be used as a marker to determine whether the patient responds to EZH2 inhibition, which is of great importance for clinical use in the treatment of this disease.
Translator: Elahe Zarei