Androgen activity in the normal male embryonic hindbrain drives lethal PFA ependymoma

Dr. Jiao Zhang, Ph.D. – Baylor College of Medicine, Houston TX

PFA ependymoma is a rare and aggressive childhood brain tumor that primarily affects infants. PFA ependymoma has a much higher incidence and worse prognosis in males than in females, but the reasons behind this difference are not well understood. Our research aims to uncover why males are more affected by PFA ependymoma and why they have worse outcomes.  

Our preliminary study of a single cell RNA sequencing cohort has shown that the cellular hierarchy of male PFA is less differentiated than female PFA. Using a special mouse model, four core genotype (FCG), we were able to separate the effects of sex hormones from genetic differences in sex chromosomes. Our preliminary data has shown that increasing androgen levels stimulate the growth of PFA ependymoma; while blocking androgens reduces the growth of PFA ependymoma. This suggests that androgen signaling in both the normal developing hindbrain, and PFA ependymoma are both necessary and sufficient to promote growth and delay differentiation.

These findings point to a new potential treatment strategy: targeting androgen receptor activity could be an effective way to slow down or stop the growth of PFA ependymoma. Developing anti androgen therapies could provide a much-needed treatment option for this currently untreatable childhood cancer, potentially improving outcomes for affected children, especially males.