Trends in Cancer
ReviewTargeting Androgen/Estrogen Receptors Crosstalk in Cancer
Section snippets
ERβ and AR Communicate in Breast and Prostate Cancers
Owing to the endocrine nature of breast and prostate carcinogenesis, targeting of hormone receptors (HRs) remains a treatment cornerstone. Estrogen (ER; ERα and ERβ) and androgen receptor (AR, see Glossary) are members of the steroid nuclear receptor superfamily [1].
In breast and prostate cancers, activation of ERα and AR, respectively, is responsible for enhanced cell proliferation and cell survival, whereas activated ERβ acts as a tumor suppressor [2]. Hence, androgen deprivation therapy
Breast Cancer
Five molecular breast cancer subtypes were identified by microarray gene expression: luminal A, luminal B, basal-like, ERBB-2-enriched, and claudin-low 12, 13. TNBC is defined by the absence of ER, progesterone receptor (PR), and ERBB-2. Although the majority of TNBCs have been classified as basal-like, these two categories are not considered synonymous [14]. Further analysis of TNBCs led to the identification of six subgroups: basal-like 1 and basal-like 2 (BL1, BL2), mesenchymal (M),
Targeting AR in Prostate Carcinogenesis
AR-targeted therapy has evolved since the discovery of prostate cancer dependence on androgen [64] and luteinizing hormone-releasing hormone (LHRH) agonists [65]. The ‘flare’ of testosterone associated with LHRH agonists subsequently led to the development of LHRH antagonists [66], but a paradigm shift in CRPC treatment was abiraterone acetate, an inhibitor of androgen biosynthesis (Table 1) [3]. Likewise, first-generation antiandrogens are initially effective but eventually develop agonist
Targeting AR in Breast Carcinogenesis
AR is expressed in approximately 80% and 60% of primary and metastatic breast carcinomas, respectively [83] and its expression varies across different subtypes 10, 84. An oncogenic role for AR was first described in molecular apocrine breast cancer, an ERα(–)/AR(+) subtype that has a steroid response signature similar to that of ERα(+) breast tumors [85]. Pharmacological modulation of AR was tested in breast cancer with contradictory results. Testosterone was used in nonselected breast cancer
Novel Technologies for Hormone Receptor-Directed Cancer Therapeutics
Modulation of HR activity is quantitatively analyzed by assaying target gene transcription or downstream cascades with various techniques. However, these parameters are indirect and are the result of HR interaction with several TCRs. To study these interactions, methods such as intermolecular free length, yeast two-hybrid, phage display, and colocalization studies in fluorescence microscopy have been employed. One major drawback of these methods is the restriction to study a single
Concluding Remarks
In cancer development and progression, ERα has a well-established role in promoting estrogen-dependent breast tumor growth, whereas ERβ significantly attenuates cell proliferation and progression in a number of cancer types, including breast and prostate. The identification of ERβ isoforms generated new data regarding the role of this receptor in tumor pathogenesis, evolution, and treatment. There are also various potential mechanisms by which ERβ isoforms can modulate AR activity during
Glossary
- Androgen receptor (AR)
- a nuclear receptor that is activated upon binding the androgenic hormone (testosterone, dihydrotestosterone) in the cytoplasm and then translocates into the nucleus, stimulating transcription of androgen responsive genes. AR plays a key role in prostate and breast cancer.
- Castration-resistant prostate cancer (CRPC)
- prostate cancer that has undergone enough molecular changes to become resistant to hormone therapy (androgen ablation); however, AR signaling is maintained in
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2021, Biosafety and HealthCitation Excerpt :Malignant tumours are often characterized by high concentrations of androgen receptors and certain hormone receptor-amplified types of breast cancer tend to possess higher concentrations [59]. Tamoxifen is a drug used to treat hormone receptor-positive breast cancers as it prevents the binding of androgens to their receptor by binding there itself [60] and this makes it a potential drug candidate for the management of COVID-19. Toremifene is another drug candidate for SAR-CoV-2 treatment.
Androgen receptor in breast cancer: A wolf in sheep's clothing? A lesson from prostate cancer.
2020, Seminars in Cancer BiologyCitation Excerpt :In parallel, also in ER- and PgR-positive BC cells AR seems to compete [26]. Instead, in PgR-negative BC cells, AR increases the ER gene transcription providing a protumorigenic role [27]. The AR/ER ratio has been reported to impact prognosis and response to antiestrogen endocrine therapy.
Estrogen Receptor Signaling in the Immune System
2023, Endocrine ReviewsVeratramine Inhibits the Cell Cycle Progression, Migration, and Invasion via ATM/ATR Pathway in Androgen-Independent Prostate Cancer
2023, American Journal of Chinese Medicine
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These authors contributed equally