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‘Toxic Masculinity’: What Is Known about the Role of Androgen Receptors in Head and Neck Squamous Cell Carcinoma

Čonkaš, Josipa; Sabol, Maja; Ozretić, Petar (2023) ‘Toxic Masculinity’: What Is Known about the Role of Androgen Receptors in Head and Neck Squamous Cell Carcinoma. International journal of molecular sciences, 24 (4). ISSN 1422-0067

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Head and neck squamous cell carcinoma (HNSCC), the most prevalent cancer in the head and neck region, develops from the mucosal epithelium of the upper aerodigestive tract. Its development directly correlates with alcohol and/or tobacco consumption and infection with human papillomavirus. Interestingly, the relative risk for HNSCC is up to five times higher in males, so it is considered that the endocrine microenvironment is another risk factor. A gender-specific risk for HNSCC suggests either the existence of specific risk factors that affect only males or that females have defensive hormonal and metabolic features. In this review, we summarized the current knowledge about the role of both nuclear and membrane androgen receptors (nAR and mARs, respectively) in HNSCC. As expected, the significance of nAR is much better known ; it was shown that increased nAR expression was observed in HNSCC, while treatment with dihydrotestosterone increased proliferation, migration, and invasion of HNSCC cells. For only three out of five currently known mARs—TRPM8, CaV1.2, and OXER1—it was shown either their increased expression in various types of HNSCC or that their increased activity enhanced the migration and invasion of HNSCC cells. The primary treatments for HNSCC are surgery and radiotherapy, but targeted immunotherapies are on the rise. On the other hand, given the evidence of elevated nAR expression in HNSCC, this receptor represents a potential target for antiandrogen therapy. Moreover, there is still plenty of room for further examination of mARs’ role in HNSCC diagnosis, prognosis, and treatment.

Item Type: Article
Uncontrolled Keywords: head and neck squamous cell carcinoma ; HNSCC ; androgen receptor ; AR ; membrane androgen receptors ; CaV1.2 ; OXER1 ; TRPM8
Subjects: NATURAL SCIENCES > Biology
Divisions: Division of Molecular Medicine
Project titleProject leaderProject codeProject type
Regulacija GLI koda u tumorima ovisnim o BRAF/NRAS mutacijamaSabol, MajaIP-2018-01-4889HRZZ
Depositing User: Petar Ozretić
Date Deposited: 16 Jun 2023 09:50
DOI: 10.3390/ijms24043766

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