Scientists have identified a key biological driver of one of the most lethal brain tumours in young children, in findings that could open the door to repurposing existing cancer drugs for a disease that currently has no targeted treatments.
The study, published in Nature and led by researchers at Baylor College of Medicine, Texas Children’s Hospital, McGill University and the University of Pittsburgh, centres on posterior fossa type A (PFA) ependymoma — a rare but highly aggressive tumour that arises at the base of the brain, predominantly in young boys.
Clinicians have long observed that PFA ependymoma is both more common in male patients and associated with worse outcomes compared to girls, but the reasons for this disparity have remained poorly understood. The new research points to androgens — male sex hormones — as the critical factor.
Unlike most cancers, PFA ependymoma is not driven by well-defined genetic mutations, which has made developing precision therapies particularly challenging. Rather than pursuing a genetic explanation for the sex differences in outcomes, the research team investigated whether hormonal signalling could be responsible.
Using animal models and patient-derived tumour cells, they found that chromosomal differences between males and females had no meaningful effect on tumour behaviour. Androgen signalling, however, did — keeping tumour cells in an immature, highly proliferative state that drives aggressive growth. Female sex hormones had no equivalent effect.
When the team increased androgen exposure in tumour models, growth accelerated. When androgen signalling was blocked, proliferation slowed — suggesting the pathway is not merely associated with tumour growth but actively required to sustain it.
“Our data has shown that increasing androgen levels stimulate the growth of PFA ependymoma, while blocking androgens reduces it,” said Dr Jiao Zhang of Baylor College of Medicine. “This suggests that androgen signalling is necessary and sufficient to promote growth and delay differentiation.”
The findings carry immediate therapeutic implications. Drugs that suppress androgen signalling are already in widespread clinical use for prostate cancer, raising the prospect of testing them in children with this tumour without the delays typically involved in developing entirely new compounds. The researchers also note that the effect appears specific to PFA ependymoma rather than brain tumours more broadly, which could allow for more targeted use.
The authors say the work also offers a broader lesson for cancer research — that hormonal and developmental influences deserve greater attention in tumours where genetic targets remain elusive, and where unexplained differences in outcomes between male and female patients have long been observed.