The epidermal growth factor receptor (EGFR) is a transmembrane tyrosine kinase receptor that plays a critical role in regulating cell proliferation, survival, and differentiation. Aberrant activation or overexpression of EGFR has been observed in several cancers, including prostate cancer (PCa), and is associated with aggressive tumor behavior and poor prognosis. The development and progression of PCa largely depend on the involvement of androgen receptor (AR) pathways, which are directly related to EGFR signaling. Research indicates that EGFR can affect AR activity, increasing transcriptional activity or promoting ligand-independent activation, which may lead to castration-resistant prostate cancer (CRPC). Furthermore, emerging evidence suggests that estrogen receptors (ERs) may also interact with EGFR signaling in prostate tissue. These may influence tumor growth, interactions with cellular plasticity, and therapy resistance, but their exact mechanisms require further investigation. Identifying and improving treatment strategies for advanced and treatment-resistant PCa requires understanding the interplay between the EGFR, AR, and ER pathways. However, clinical trials have shown limited success in targeting EGFR alone, possibly through compensatory mechanisms via steroid hormone receptors. Therefore, therapies that simultaneously target EGFR and AR/ER activity may be more effective. Continued research into the molecular interplay between these pathways will broaden our understanding of prostate cancer biology and support the development of more personalized and effective treatments. In this review will focus on EGFR/HER1 and its putative role in prostate cancer. Furthermore, we discuss the potential interaction between EGFR, androgen receptor (AR), and estrogen receptor (ER) signaling pathways.
G. M. Gonçalves, D. S. Souza, C. Costa et al.· Journal of Steroid Biochemis...· 0 citations
Abstract Prostate cancer is the second most common cause of cancer in men worldwide, and first-line therapies for metastatic disease include androgen deprivation therapy and androgen receptor pathway inhibitors, in addition to chemotherapy for selected patients. Although these strategies improve patient prognosis, progression to castration-resistant prostate cancer and therapeutic resistance remain clinically significant. In this review, we will explore published and new evidence of the expression and function of estrogen receptors (ERs) ERα and ERβ, as well as their variants, and the G protein-coupled estrogen receptor (GPER) in normal prostate gland, during development and adulthood and in prostate cancer cell lines. Consistent with these findings, studies from the literature have demonstrated that ERα, ERβ, and GPER are expressed in a cell-specific manner in the normal prostate gland. In the androgen-independent prostate cancer cells PC-3 (derived from bone metastasis) and DU-145 (brain metastasis), used in vitro and in xenograft implants as castration-resistant prostate cancer models, ERα and ERβ are present at transcript and protein levels, as well as the GPER. Importantly the presence of ERα36 splice variant is also detected in prostate cancer cells. Although the exact contributions of these modifications to prostate cancer advancement and treatment outcomes remain under investigation, the absence of selective inhibitors for the resulting ER variant proteins restricts deeper inquiry. Developing such targeted agents is crucial to uncovering variant biology in both healthy and malignant tissues, evaluating their therapeutic value in preclinical settings, and ultimately guiding clinical management.
D. S. Souza, Camila Rebelo Morgado Costa, Larissa Thainá Brito Dias et al.· Journal of the Endocrine Soc...· 0 citations
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