World-first research published today by 爆料王 scientists has uncovered a mechanism that may explain why glioblastoma returns after treatment, offering new clues for future therapies which they will now investigate as part of an Australian industry collaboration.听
Glioblastoma is one of the deadliest brain cancers, with a median survival rate of just听. Despite surgery and chemotherapy, more than 1250 clinical trials over the past 20 years have struggled to improve survival rates.
Published in听, the study shows that a small population of drug-tolerant cells known as 鈥減ersister cells鈥 rewires its metabolism to survive chemotherapy, using an unexpected ally as an invisibility cloak: a fertility gene called PRDM9.
鈥淭his is a world-first discovery that changes what we know about glioblastoma,鈥 said lead author听Professor Lenka Munozfrom the听Charles Perkins Centre听at the 爆料王. 鈥淏y uncovering how these cancer cells recruit a fertility gene to survive treatment, we鈥檝e opened the door to new approaches that we hope could lead to safer, more effective therapies.鈥
The researchers are now working with Australian biotech company Syntara to develop PRDM9 inhibitors for further testing in animal models, with the hope to eventually progress to human studies. The next steps are to determine whether these inhibitors can eliminate persister cells and prevent glioblastoma from returning. Trialling this in humans is likely several years away, pending successful completion of preclinical safety and efficacy studies.听
Accounting for about听, glioblastoma claims the lives of up to听听and around听. Even after surgery, radiation and chemotherapy,听. Clinicians call this 鈥渕inimal residual disease鈥, meaning the few hidden cancer cells that survive treatment eventually regrow the tumour.听
鈥淔or patients and their families facing glioblastoma, recurrence is inevitable. This research offers hope for new strategies in the future where none existed,鈥 said Professor Munoz, who co-led the study with听Dr George Joun听from the听School of Medical Sciences听in the听Faculty of Medicine and Health.
How glioblastoma uses a fertility gene to cheat chemotherapy
The researchers found that while the body undergoes chemotherapy stress, glioblastoma cells are able to hijack PRDM9 to churn out cholesterol, helping persister cells withstand damage and eventually allowing the tumour to return. Previously, PRDM9 was only known as a fertility gene, active in reproductive cells at the very start of egg and sperm formation, long before fertilisation.听
鈥淐hemotherapy kills most cancer cells, but in glioblastoma a few survive and are able to regrow the tumour. We think we鈥檝e found their survival trick and potential ways to block it,鈥 said Professor Munoz.听
Chemotherapy kills most cancer cells, but in glioblastoma a few survive and are able to regrow the tumour. We think we鈥檝e found their survival trick and potential ways to block it.
Professor Lenka Munoz
Faculty of Medicine and Health
Researchers hope new treatment strategy could prevent glioblastoma relapse
By blocking PRDM9 or cutting off cholesterol supply, researchers were able to wipe out persister cells in lab and animal models. When combined with chemotherapy, their approach dramatically improved survival in mice.听
The team also developed a new brain-penetrant chemotherapy drug, WJA88, and paired it with a cholesterol-lowering agent already tested in humans. This combination shrank tumours and extended survival in preclinical models with minimal side effects.听
鈥淧RDM9 isn鈥檛 active in most normal tissues, which makes it an incredibly selective and promising target for cancer therapy,鈥 said Dr Joun, first author and Research Fellow in the School of Medical Sciences. 鈥淚f we can eliminate the last cancer cells standing, we can stop glioblastoma from returning. That would be a game changer for patients and families.鈥
Potential implications for other hard-to-treat cancers
The researchers say this is the first time PRDM9 has been linked to cancer, potentially opening the door to safer, more targeted treatments. Professor Munoz and her team believe the same mechanism may exist in other hard to treat cancers, with plans to test the approach on ovarian cancer next.
鈥淐ancer relapse is one of the biggest challenges in oncology. Our research shows that by directly targeting persister cells, relapse may be preventable in preclinical models,鈥 said Professor Munoz.
Experts hope the discovery could reshape cancer research and treatment globally.
鈥淲e now need to look beyond the bulk of the tumour and study rare persister cells that drive recurrence, as well as what happens after treatment ends rather than only during drug exposure,鈥 said Professor Munoz.
Research
Munoz, Lenka, Joun, George, et al., , (Nature Communications, 2025)
DOI: 10.1038/s41467-025-65888-5
Declaration
Please note that the scientific study represented in this media release is entirely separate from, and unrelated to, the experimental immunotherapy treatment developed by Professor Georgina Long, which was detailed in听Nature Medicine听in 2025.
The research was funded by the NHMRC, Tour de Cure, Arto Hardy family, and an Australian Government RTP Scholarship.
Professor Lenka Munoz is an inventor on two patents related to the discovery and development of brain permeable microtubule-targeting agents, including CMPD1 and WJA88 used in this study. Professor Munoz and Dr Joun are inventors on PCT/AU2024/050979 which covers the drug combinations described in this study for therapeutic use in cancer.
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