What's Happening?
Research from the University of Sydney has identified a fertility-linked gene, PRDM9, that helps glioblastoma cells resist chemotherapy. Glioblastomas, known for their high mortality rate, often recur after treatment. The study found that a subset of drug-tolerant
cells, called persister cells, use PRDM9 to rewire their metabolism and survive chemotherapy. By blocking PRDM9 or cutting off cholesterol supply, researchers were able to eliminate these cells in models, suggesting a new therapeutic target. The study also developed a brain-penetrant chemotherapy drug, WJA88, paired with a cholesterol-lowering agent, showing promising results in preclinical models.
Why It's Important?
The identification of PRDM9 as a key player in chemotherapy resistance offers a new avenue for treating glioblastoma, one of the deadliest brain cancers. Targeting PRDM9 could lead to more effective therapies, potentially preventing tumor recurrence and improving patient survival rates. The research highlights the importance of understanding the mechanisms behind drug resistance, which could be applicable to other hard-to-treat cancers. By focusing on persister cells, the study opens the door to novel strategies that could enhance the efficacy of existing treatments and reduce cancer relapse.
What's Next?
The research team plans to further develop PRDM9 inhibitors in collaboration with biotech company Syntara, aiming to conduct human studies in the future. Additionally, the scientists intend to explore the role of persister cells in other cancers, such as ovarian cancer, to determine if similar mechanisms of drug resistance are at play. These efforts could lead to broader applications of the findings, potentially transforming treatment approaches for various cancers and improving long-term outcomes for patients.
