Sex-Specific Sub-typing of Glioblastoma

Multiple strategies have been used in an attempt to better stratify patients with GBM. These have included classification of tumors based on molecular subtypes, tumor cell of origin, mutational spectrum, and chromosomal and genomic structural variation. Despite these efforts, there has been little significant improvement in survival of patients with GBM. While familial predisposition syndromes cause a small fraction of brain tumors, the etiology of the majority of brain tumors is unknown. Environmental factors may play a role, but incidence rates of brain tumors are consistent across different regions of the world.  Despite this, brain tumors are more predominant in males than females, regardless of patient age, and females with GBM respond to treatment better than their male counterparts. Sex differences in incidence and outcome likely reflect some aspect of the influence of sex on mechanisms driving tumor formation and propagation.

We are collaborating with scientists in multiple departments at Washington University, as well as at other institutions, to develop novel computational algorithms that, when applied to transcriptome-level data and patient outcome, can be used to identify sex-specific subtypes of GBM. With these algorithms we can begin to address how biological mechanisms of GBM differ in males and females, and how these impact on survival and response to therapy. We believe these studies will provide an important foundation for developing personalized treatment strategies for male and female GBM patients, and may lead to the identification of new prognostic markers and novel, more efficacious therapeutic targets in GBM.