Breakthrough in the fight against ovarian cancer: enzyme responsible for chemotherapy resistance discovered

Northwestern Medicine researchers have identified the enzyme PRMT5 as a key factor in chemotherapy resistance in advanced ovarian cancer, a discovery that could pave the way for new, more effective treatments.

Ovarian cancer remains one of the leading causes of cancer deaths among women in the U.S. Although treatment has improved significantly, many women still have relapses and no longer respond to chemotherapy . As Professor Mazhar Adli of Northwestern University explains, “ chemoresistant cancer is the greatest clinical challenge physicians face in treating this type of cancer .”

Adli’s team discovered that the enzyme PRMT5 plays a major role in this resistance . PRMT5 regulates gene expression and has previously been found to be elevated in treatment- resistant cancers . The researchers used advanced techniques, including immunostaining and CRISPR screening, to better understand its function.

Researchers have shown that the protein KEAP1 normally controls PRMT5 levels, contributing to its breakdown. However, in cancers, this mechanism stops working. " Chemotherapy causes stress in cells , KEAP1 is suppressed, and then PRMT5 is upregulated," Adli explains. As a result, cells become more resistant to treatment .

The most important step in the study was to test a therapy combining PRMT5 inhibitors with chemotherapy . In a mouse model of ovarian cancer, this combination significantly increased cancer cell death and limited tumor growth . "We showed that this is a really therapeutically useful target," emphasizes Adli.

Scientists now want to move on to the next stage – clinical trials involving humans. According to Adli, testing PRMT5 inhibitors alone may not be effective enough, but combining them with chemotherapy offers huge therapeutic potential. If further studies confirm the effectiveness of this method, it could be a breakthrough in the treatment of ovarian cancer .