Androgen receptor in salivary gland carcinoma: A review of an old marker as a possible new target

Yeoh, Chit Cheng; Dabab, Nedal; Rigby, Elyse; Chhikara, Ritu; Akaev, Iolia; Gomez, Ricardo Santiago; Fonseca, Felipe Paiva; Brennan, Peter A.; Rahimi, Siavash

doi:10.1111/jop.12741

Cited by 21 publications

(8 citation statements)

References 59 publications

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“…In this case, salivary CORT may act as a paracrine or autocrine factor in the glands. As SG cells and oral cavity tissues express receptors for steroid hormones (41–43), CORT and TS may act through these receptors in these putative target tissues. They may affect the activities in the site specific cells in the SGs and then regulate the component fluctuation of saliva as reported in the intestine (14, 16) and in the skin (17).…”

Section: Discussionmentioning

confidence: 99%

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

et al. 2019

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Extra-adrenal steroid hormone production has been reported in several tissues, the biological role of which is interesting in terms of hormonal regulation of metabolism, growth, and behavior. In this report, we describe for the first time steroidogenesis in rat salivary glands. Enzyme activities associated with corticosterone and testosterone production were detected in rat salivary glands by LC-MS analysis. In tissue homogenates of rat salivary glands, progesterone was produced enzymatically in vitro from pregnenolone in the presence of NADPH and NADH. Deoxycorticosterone was produced from progesterone, corticosterone from deoxycorticosterone, and testosterone from androstenedione (but not pregnenolone from cholesterol) via enzymatic reactions using the same tissue homogenates. Immunoblotting analysis indicated the expression of 11β-hydroxylase (cytochrome P450 11β1; CYP11β1), which mediated the production of corticosterone from deoxycorticosterone. However, CYP family 11 subfamily A member 1 (CYP11A1)-mediated production of pregnenolone from cholesterol was not detected in the salivary glands by immunoblotting using a specific antibody. These results indicate that corticosterone and testosterone are produced from pregnenolone in rat salivary glands. The initial substrate in salivary steroidogenesis and the roles of salivary corticosterone and testosterone are discussed.

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Section: Discussionmentioning

confidence: 99%

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

et al. 2019

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“…The treatment of choice for salivary gland carcinomas is surgery with adjuvant radiotherapy. However, there are subtypes with rapid progression that complicate surgery and that, until recently, could only be treated with palliative chemotherapy [ 48 ]. Currently, androgen receptors, HER-2 and NTRK are recommended as possible therapeutic targets.…”

Section: Salivary Gland Tumoursmentioning

confidence: 99%

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: a consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

Trigo¹,

García‐Cosío²,

García‐Castaño

et al. 2022

Clin Transl Oncol

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The treatment of head and neck and salivary gland tumours is complicated and evolves constantly. Prognostic and predictive indicators of response to treatment are enormously valuable for designing individualized therapies, which justifies their research and validation. Some biomarkers, such as p16, Epstein–Barr virus, PD-L1, androgen receptors and HER-2, are already used routinely in clinical practice. These biomarkers, along with other markers that are currently under development, and the massively parallel sequencing of genes, ensure future advances in the treatment of these neoplasms. In this consensus, a group of experts in the diagnosis and treatment of tumours of the head and neck and salivary glands were selected by the Spanish Society of Pathology (Sociedad Española de Anatomía Patológica—SEAP) and the Spanish Society of Medical Oncology (Sociedad Española de Oncología Médica—SEOM) to evaluate the currently available information and propose a series of recommendations to optimize the determination and daily clinical use of biomarkers.

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“…The expression patterns of sex hormone receptors in HNSCC is also unclear, which is unsurprising considering these difficulties and the heterogeneity of these tumours. Androgen receptor was found to be expressed in salivary gland duct carcinomas and other non-squamous head and neck cancers, as recently reviewed (71). The present review will focus on data concerning HNSCC.…”

Section: Hormone Receptors In Hnsccmentioning

confidence: 95%

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis

et al. 2021

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Background/Aim: Head-and-neck squamous cell carcinoma (HNSCC) is the fifth most common cancer in the world and human papillomavirus (HPV) is an important risk factor for this neoplasm. Recent studies showed an association between sex hormone receptors and pathogenesis and/or prognosis in patients with HNSCC. The aim of this study was to clarify the expression patterns of sex hormone receptors in HPV-positive and HPV-negative HNSCC and their associations with tumour biopathology and biological behaviour. Materials and Methods: Scientific literature indexed in PubMed about sex hormone receptors in HNSCC was retrieved and critically analyzed, to obtain an overview of expression patterns and their possible implications for tumour biopathology and prognosis. Results: Sex hormone receptors were more frequently detected in oropharyngeal tumours compared with HNSCC from other locations. ERα was associated with HPV-positive tumours. The androgen and progesterone receptors were associated with poor patient prognosis. Estrogen receptor alpha (ERα) is implicated in the biopathology of HNSCC in different ways, by promoting DNA hypermutation and facilitating HPV integration thus contributing to an immunogenic phenotype, but also by cooperating with the epithelial growth factor receptor (EGFR) to promote resistance to therapy. Conclusion: The expression of sex hormone receptors may be of prognostic value in specific tumour subgroups, but the use of hormonal therapies for HNSCC is still not in close sight.Head-and-neck cancer comprises a group of malignancies affecting multiple sites including the oral cavity, the oropharynx, nasopharynx, hypopharynx, larynx and the salivary glands. Histologically, these lesions are most commonly squamous cell carcinomas (HNSCC) (1). An estimated 650,000 new cases occur yearly worldwide, along with 330 000 deaths from HNSCC (2). In the USA, HNSCC corresponds to 3% of all cancers with approximately 53,000 new cases and 10,800 deaths yearly. Males seem to be at higher risk, with a male to female ratio varying between 2:1 and 4:1 (3). Classically, alcohol and tobacco consumption have been identified as major risk factors for developing HNSCC (4, 5). Recently, infection with high-risk human papillomavirus (HPV) has been recognized as a risk factor for developing HNSCC (6). HPVpositive HNSCC is preferentially located at oropharyngeal sites, especially the tonsils and the tongue base, and shows distinguishing clinico-pathological features (7). Other risk factors for developing HNSCC include dietary or workplace exposure to environmental toxicants and genetic predisposition (8-10). Between 2005 and 2014, the incidence of HPV-positive HNSCC increased by 3% while that of classical lesions decreased by 2% (11). The increasing incidence of HPVpositive HNSCC motivated a significant effort to understand the biopathology of these lesions and adapt the current therapeutic approaches (12). A number of markers is currently in use or under study for identifying these lesions (e.g., immunohistochemistry for p16 IN...

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Androgen receptor in salivary gland carcinoma: A review of an old marker as a possible new target

Cited by 21 publications

References 59 publications

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

Analysis of Corticosterone and Testosterone Synthesis in Rat Salivary Gland Homogenates

Recommendations for the use of biomarkers for head and neck cancer, including salivary gland tumours: a consensus of the Spanish Society of Medical Oncology and the Spanish Society of Pathology

Is There a Role for Sex Hormone Receptors in Head-and-neck Cancer? Links with HPV Infection and Prognosis

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