An international team led by researchers from Baylor College of Medicine, Texas Children’s Hospital, McGill University, and the University of Pittsburgh School of Medicine has discovered what drives the growth of a deadly childhood brain tumor called posterior fossa type A (PFA) ependymomas.
The researchers report in the journal nature Androgens, commonly known as male hormones, promote the growth of PFA ependymomas, but not other brain tumors. Importantly, blocking androgen signaling reduces tumor growth. This discovery opens up new therapeutic approaches to this currently untreatable childhood cancer.
“The cause of PFA ependymoma growth has remained a mystery for quite some time,” said co-lead author Dr. Zhao Zhang, assistant professor of pediatrics-hematology/oncology at Baylor and Texas Children’s Hospital. “In contrast to other deadly brain tumors, this cancer lacks a clear genetic driver, which has slowed the development of effective treatments. In this study, we investigated this tumor from a different angle.”
Previous studies have shown that most patients with PFA ependymomas are male, and their survival rate is lower than that of women. However, the mechanisms underlying these sex differences remain unclear. It is also known that female brain cells appear to be more developed than male brain cells in populations at the same early developmental stage.
“Gender differences play an important role in cancer growth,” Zhang says. “We decided to study whether sex differences could explain why boys are more vulnerable to PFA ependymomas than girls. Understanding how sex-specific factors contribute to PFA tumor progression and treatment response may help develop better treatments to improve survival and quality of life for affected children.”
Using animal models and cancer cells grown in the laboratory, the research team investigated whether the observed sex differences in susceptibility to PFA ependymomas depend on sex chromosomes (XX in women and XY in men) or sex hormones (androgens in men and estradiol or progesterone in women).
“Because PFA ependymoma cells develop in normal brain cells, we found that they occur less frequently in male patients than in female patients,” Zhang said. “This difference is caused by androgens, which keep these tumor cells less developed and more prone to growth. No differences due to chromosomal factors were observed, and female hormones did not alter the growth of PFA cells compared to controls.”
Further studies supported this observation by showing that androgen supplementation promoted the growth and enhanced the underdeveloped characteristics of PFA ependymomas.
“Our study provides a biological basis for understanding the long-recognized sex differences in PFA ependymomas,” said co-author Dr. Claudia Kleinman, professor and research associate in the Department of Human Genetics at McGill University’s Lady Davis Medical Research Institute.
“We uncover a previously unknown link between early hormone exposure and tumor formation, suggesting that antiandrogen therapy may be a promising treatment option for this devastating disease,” said co-author Klandai Manuvel Anthony Michaelraj, MD, assistant professor of neurosurgery at the University of Pittsburgh School of Medicine.
“Our findings have potential clinical implications because they suggest that androgen blockade therapy may represent a rational direction for future targeted treatment strategies,” said co-author Michael D. Taylor, Ph.D., professor of pediatrics, hematology/oncology and neurosurgery at Baylor University and staff neurosurgeon at Texas Children’s Hospital.
sauce:
Baylor College of Medicine
Reference magazines:
DOI: 10.1038/s41586-026-10264-6
