SYDNEY, Dec. 16 (Xinhua) -- Scientists in Australia have uncovered a mechanism that may explain why glioblastoma, one of the deadliest brain cancers, returns after treatment, offering new clues for safer, more effective therapies, a media release of the University of Sydney said Tuesday.
The study, published in Nature Communications, shows that a small population of drug-tolerant cells known as "persister cells" rewires its metabolism to survive chemotherapy, using an unexpected ally as an invisibility cloak: a fertility gene called PRDM9.
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 tumor to return, it said.
"Chemotherapy kills most cancer cells, but in glioblastoma, a few survive and are able to regrow the tumor. We think we've found their survival trick and potential ways to block it," said lead author Professor Lenka Munoz from the University of Sydney.
By blocking PRDM9 or cutting off the cells' 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, the release said.
The team developed a brain-penetrant chemotherapy drug WJA88, paired with a tested cholesterol-lowering agent. The combination shrank tumors and extended survival in preclinical models with minimal side effects, it said, adding the same mechanism may exist in other hard-to-treat cancers, with plans to test the approach on ovarian cancer next.
Accounting for about half of all brain tumors, glioblastoma claims the lives of up to 200,000 people globally each year, with a median survival rate of just 15 months. ■