Targeting androgen receptor in glioblastoma

Abstract

Glioblastomas are primary brain tumors that originate from glial stem cells or progenitor cells. There is a large difference in the incidence of glioblastoma between males and females. Studies revealed that the gender differences in the tumor may be attributable to the androgen receptor signaling axis. The incidence rate of glioblastoma in men is higher than that in women. Aberrant activation of the androgen receptor signaling pathway, or interactions between the androgen receptor signaling axis and other signaling axes promote the development of glioblastoma. Therefore, targeting the androgen receptor holds promise as a therapeutic approach for glioblastoma. This review investigates the dynamics of drug research into the treatment of glioblastoma by targeting the androgen receptor. The first finding in line with expectations is that androgen receptor antagonists, represented by enzalutamide, have been studied and shown to have anti-glioblastoma effects. In addition, it was found that the combination of 5-alpha reductase inhibitors and androgen receptor antagonists resulted in better therapeutic outcomes than each of them alone. Similar results were obtained with the combination of an epidermal growth factor receptor inhibitor and an androgen receptor antagonist. In addition, four small molecule compounds have been shown to exert significant anti-glioblastoma effects by directly or indirectly targeting the androgen receptor. Expectantly, one of these small molecules, seviteronel, progressed to the phase II clinical trial stage. These findings suggest that targeting the androgen receptor for glioblastoma may be a promising therapeutic option.

Keywords: 5α-Reductase; 5α-Reductase inhibitor; Androgen receptor; Androgen receptor antagonists; Epidermal growth factor receptor; Glioblastoma.