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Androgen Receptor (AR)

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Androgen Receptor (AR)

What is the androgen receptor (AR)?

Androgen receptors (ARs) are proteins that are normally found in small amounts in different tissues of the body [1]. The main role of ARs is to react to the hormones, testosterone and dihydrotestosterone (DHT) to control how other genes are switched on or off [2]. ARs play a crucial role in male sexual development, reproduction and the maintenance of the prostate gland, musculoskeletal system and cardiovascular system [3].

Why is it important?

Many salivary duct carcinomas (SDC) have a large amount of ARs present which drive the cancer to grow and spread [4].

What is the evidence?

ARs were found in more than 90% of SDC cases [5], and in 20%–30% of adenocarcinoma, not otherwise specified (NOS) [4].

Are ARs a target for treatment?

Yes, as these cancers rely heavily on ARs to survive, these proteins may be targeted for treatment [6, 7].

Traditional Androgen Deprivation Therapy (ADT) reduces the activity of ARs by limiting the hormones that can bind to and activate the protein. This approach involves a combination of androgen blockers such as bicalutamide, and hormone suppressors such as leuprolide and goserelin.

AR-targeted drugs developed for prostate cancer are also being trialled for salivary gland cancer [6, 8].

Useful resources

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References

  1. Ruizeveld de Winter JA, Trapman J, Vermey M, Mulder E, Zegers ND, van der Kwast TH. Androgen receptor expression in human tissues: an immunohistochemical study. J Histochem Cytochem. 1991; 39(7):927-36.
  2. Lu NZ, Wardell SE, Burnstein KL, Defranco D, Fuller PJ, Giguere V, et al. International Union of Pharmacology. LXV. The pharmacology and classification of the nuclear receptor superfamily: glucocorticoid, mineralocorticoid, progesterone, and androgen receptors. Pharmacol Rev. 2006; 58(4):782-97.
  3. Davey RA, Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev. 2016; 37(1):3-15.
  4. Dalin MG, Watson PA, Ho AL, Morris LG. Androgen Receptor Signaling in Salivary Gland Cancer. Cancers (Basel). 2017; 9(2).
  5. Nakaguro M, Tada Y, Faquin WC, Sadow PM, Wirth LJ, Nagao T. Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment. Cancer Cytopathol. 2020; 128(10):693-703.
  6. Ho AL, Foster NR, Zoroufy AJ, Campbell JD, Worden F, Price K, et al. Phase II Study of Enzalutamide for Patients With Androgen Receptor-Positive Salivary Gland Cancers (Alliance A091404). J Clin Oncol. 2022; 40(36):4240-9.
  7. Fushimi C, Tada Y, Takahashi H, Nagao T, Ojiri H, Masubuchi T, et al. A prospective phase II study of combined androgen blockade in patients with androgen receptor-positive metastatic or locally advanced unresectable salivary gland carcinoma. Ann Oncol. 2018; 29(4):979-84.
  8. Locati LD, Cavalieri S, Bergamini C, Resteghini C, Colombo E, Calareso G, et al. Abiraterone Acetate in Patients With Castration-Resistant, Androgen Receptor-Expressing Salivary Gland Cancer: A Phase II Trial. J Clin Oncol. 2021; 39(36):4061-8.

Last Updated December 2025