Innovative Drug Combinations Offer Hope for Tough-to-Treat Cancers

Researchers at Virginia Tech's Fralin Biomedical Research Institute have identified a promising new approach to combat certain resistant cancers by targeting the enzyme PRMT5. This enzyme, a naturally occurring protein, appears to be vital for the survival of some tumors, especially those lacking specific tumor suppressor genes like CDKN2A and MTAP. These genes normally help control cell growth and prevent cancer progression, but their absence makes tumors more dependent on PRMT5.

In a recent publication in Cancer Research, Assistant Professor Kathleen Mulvaney and her team demonstrated that using genetic screening techniques, including CRISPR gene editing, they uncovered effective drug combinations that inhibit PRMT5 and other related pathways. This strategy has shown significant promise in preclinical models, including cell cultures and animal studies, especially for treatment-resistant lung, brain, and pancreatic cancers. The combination therapies outperform single-drug treatments by significantly reducing tumor growth and even leading to complete tumor regression.

Many of these solid tumors share the characteristic of missing tumor suppressor genes, rendering them reliant on PRMT5. By blocking this enzyme, the cancer cells become more vulnerable, providing a new therapeutic target. Additionally, combining PRMT5 inhibitors with drugs that disrupt communication pathways like MAP kinase further enhances treatment efficacy.

The findings are particularly relevant given the low survival rates associated with these cancers. For instance, pancreatic cancer has a five-year survival rate of less than 15%, and glioblastoma is known for its aggressive resistance to treatment. The research suggests that about 5% of cancer patients—roughly 80,000 to 100,000 annually in the U.S.—could benefit from these innovative therapies. These breakthroughs not only advance our understanding of cancer biology but also open new avenues for clinical trials aimed at improving patient outcomes.

Overall, this research highlights the potential of combining targeted therapies to overcome drug resistance and improve survival rates for some of the most challenging cancers.