What's Happening?
Researchers at the University of Sydney have discovered that a fertility-linked gene, PRDM9, plays a crucial role in helping glioblastoma cells resist chemotherapy. Glioblastomas are among the deadliest
brain cancers, with a median survival rate of about 15 months. The study, published in Nature Communications, reveals that a small population of drug-tolerant cells, known as persister cells, rewire their metabolism to survive chemotherapy by utilizing the PRDM9 gene. This gene, typically active in reproductive cells, aids in generating cholesterol, which helps these cells withstand chemotherapy damage. The research team, led by Dr. Lenka Munoz, found that blocking PRDM9 or cutting off the cholesterol supply could effectively eliminate these persister cells. The study also demonstrated that combining this approach with chemotherapy significantly improved survival rates in mice models.
Why It's Important?
This discovery is significant as it opens new avenues for developing more effective cancer therapies. Glioblastomas account for about half of all brain tumors and are notorious for their high recurrence rate even after aggressive treatment. By targeting the PRDM9 gene, which is not active in most normal tissues, researchers have identified a selective and promising target for cancer therapy. The potential to prevent cancer relapse by eliminating persister cells could revolutionize treatment strategies not only for glioblastoma but also for other hard-to-treat cancers. This research underscores the importance of understanding the mechanisms behind cancer cell survival and recurrence, which could lead to safer and more effective therapies.
What's Next?
The research team is collaborating with the Australian biotech company Syntara to develop PRDM9 inhibitors for further testing in animal models. They aim to conduct human studies in the coming years. Additionally, the researchers plan to explore whether other difficult-to-treat cancers, such as ovarian cancer, also utilize persister cells to survive chemotherapy. This could broaden the application of their findings and potentially lead to breakthroughs in treating various types of cancer. The development of a brain-penetrant chemotherapy drug, WJA88, paired with a cholesterol-lowering agent, has already shown promise in preclinical models, indicating a potential path forward for clinical trials.
