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Targeting androgen receptor in glioblastoma

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ELSEVIER SCIENCE INC
DOI: 10.1016/j.critrevonc.2023.104142

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Glioblastoma; Androgen receptor; 5 alpha-Reductase; Epidermal growth factor receptor; Androgen receptor antagonists; 5 alpha-Reductase inhibitor

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Glioblastomas, a type of brain tumor, have a higher incidence in males compared to females, and this difference may be attributed to the androgen receptor signaling axis. Drug research targeting the androgen receptor for the treatment of glioblastoma has shown that androgen receptor antagonists, in combination with other drugs, can have anti-tumor effects. Additionally, small molecule compounds targeting the androgen receptor have also shown promising results in reducing glioblastoma growth.
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 glio-blastoma 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 glio-blastoma. 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.

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