New Research Identifies Enzyme PRMT5 as a Key Factor in Chemotherapy Resistance in Ovarian Cancer

Scientists from Northwestern University have uncovered a significant mechanism behind the development of chemotherapy resistance in advanced ovarian cancer. Published in the Journal of Clinical Investigation, the study reveals that elevated levels of the enzyme PRMT5 contribute to the resistance, making standard treatments less effective. Ovarian cancer remains one of the leading causes of cancer-related deaths among women in the United States, and overcoming drug resistance is a central challenge in improving patient outcomes.

The research team, led by Dr. Mazhar Adli, discovered that PRMT5 is normally kept in check by the protein KEAP1, which tags PRMT5 for degradation under regular conditions. However, in resistant tumors, this regulation breaks down, resulting in abnormally high levels of PRMT5. This enzyme influences stress response genes, creating a cellular environment that promotes drug resistance.

Using advanced techniques like CRISPR screening and intracellular immunostaining, the researchers demonstrated that inhibiting PRMT5 can increase cancer cell death. Combining PRMT5 inhibitors with chemotherapy drugs significantly reduced tumor growth in mouse models, indicating a promising therapeutic avenue.

The study also highlights that stress conditions caused by chemotherapy suppress KEAP1 activity, leading to the upregulation of PRMT5. This finding suggests that targeting the PRMT5 pathway could help overcome resistance. The researchers propose that initiating clinical trials to evaluate combination therapies involving PRMT5 inhibitors is the next step, as current inhibitors are already in early-phase testing.

In summary, targeting PRMT5 shows great potential as a complementary approach to enhance the effectiveness of existing ovarian cancer treatments. Future investigations and clinical trials could pave the way for new, more effective therapies against resistant ovarian cancer.