Researchers have shown that inhibition of the protein — EZH2 — can reduce the growth of cancer cells in the blood cancer multiple myeloma — a type of blood cancer where immune cells grow in an uncontrolled way in the bone marrow. According to the researchers, the disease is very difficult to treat and is still considered incurable, and thus it is urgent to identify new therapeutic targets in the cancer cells.
The mouse-model study, published in the journal Cell Death & Disease, indicates that the reduction is caused by changes in the cancer cells’ metabolism and these changes can be used as markers to discriminate whether a patient would respond to treatment by EZH2 inhibition.
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“We treated mice with a type of cancer that corresponds to human multiple myeloma with a substance that inhibits EZH2 and discovered several signs that the treated mice had slower cancer growth than non-treated mice. This provided further evidence for the potential of EZH2 as a target for clinical intervention,” said researcher Helena Jernberg Wiklund from Uppsala University in Sweden.
The results from the mouse model encouraged the researchers to further investigate what it is that makes the cells sensitive to EZH2 inhibition. Human multiple myeloma cells are more heterogeneous than mouse model cells and they found that some types of human cultivated multiple myeloma cells were sensitive whereas others were resistant. To study this phenomenon further, the researchers employed a global analysis of cellular metabolites in combination with analysis of gene activity. Sensitivity was found to be associated with alterations in specific metabolic pathways in the cells.
“In cells that were sensitive to EZH2 inhibition, the methionine cycling pathways were altered, an effect we did not detect in non-sensitive cells. This alteration was caused by a downregulation of methionine cycling-associated genes,” said Wiklund.
The alterations in metabolite abundance in the methionine cycling pathways could be used as markers to discriminate whether a patient is responding to protein EZH2 inhibition, which is of great importance for the potential clinical use of this treatment, the team said. (IANS)