Targeting sex hormone signaling: A promising therapeutic alternative for glioblastoma

Abstract

Glioblastoma is the most common and malignant primary brain tumor of the central nervous system, with conventional therapy yielding very poor results in overall patient survival and quality of life. The low life expectancy at diagnosis of just 15 months, highlights the need for novel therapeutic alternatives. Glioblastoma has a higher incidence in men than in women, suggesting a critical role of sex hormone signaling in tumor maintenance and progression. There is now ample evidence that sex hormones impact glioblastoma malignancy. Testosterone, through the androgen receptor, promotes proliferation, migration, and invasion of tumor cells. Interestingly, estradiol and progesterone show both pro- and anti-tumor effects, depending on the dose and the specific receptors expressed in the cells. Sex hormones regulate gene activity by binding to intracellular receptors, which act as ligand-activated transcription factors. Additionally, the presence of membrane receptors for estrogens and progesterone can promote rapid cellular responses, activating signaling pathways such as PI3K/AKT and MAPK in tumor cells. Thus, the regulation of sex hormone activity and receptor function can directly affect tumor progression and survival. This article analyzes the impact of sex hormone signaling on the malignancy of glioblastomas.