ABOUT PROSTATE CANCER

How androgen receptor inhibitors (ARIs) work

Published April 2022

How androgen receptor inhibitors (ARIs) work
How androgen receptor inhibitors (ARIs) work

Testosterone (T) is a hormone called an “androgen” 1

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androgen mobile

T plays a central role in normal male sexual development and affects certain behaviours. Some studies have linked this hormone to:2-4

male sexual development desktop
male sexual dev mobile
The effects of T in your body occur by activating “androgen receptors” (ARs)5. T is made in your testes and adrenal glands, and then travels through your bloodstream to reach “target cells” that lie within the prostate.5
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effect of t mobile

Inside these cells, some of the T is converted by an enzyme (“5a-reductase”) to dihydrotestosterone (DHT), which is also an androgen5

Any treatment that reduces androgens in the body is called “androgen deprivation therapy” (ADT)6

Understanding AR inhibitors (ARIs)

When T or DHT bind with an AR, the AR changes shape – this new shape means it can now enter the cell nucleus5 (the cell's control centre)

understanding ARI desktop
understanding ARI mobile

Inside the nucleus, the AR recruits other proteins to from a complex allowing it to bind to the DNA and start instructing it to make new proteins required for normal cell activity5

You may be wondering why this is important?

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  • Hormones like T and DHT also control the growth of cells in the prostate6-8 - prostate cancer tumours depend on them for growth and disease progression6,9,10
  • AR activity in prostate cancer cells is abnormally high in mutated cancer cells.8 Therefore, disease progression is mainly driven by AR activity.11
  • So, if you can block the AR activity, you can reduce the growth and progression of prostate cancer tumour cells.8

This is where "androgen receptor inhibitors" (ARIs) come in

Medicines like enzalutamide are ARIs – they bind directly to ARs in your cells and block them from binding with T or DHT or prevent the activity of bound ARs. This can significantly slow down the growth of the tumour cells and extend the life of men with prostate cancer.6,11 Your doctor may refer to these medicines as 'hormone therapy', i.e. drugs that affect the action of hormones.
Enzalutamide is a “second-generation non-steroidal anti-androgen” (2L NSAA)11 it works in three distinct ways:6,11,12
  1. Enzalutamide competes with T/DHT to block them from binding to the AR, preventing the action of T/DHT in cell growth.
     
  2. Enzalutamide also blocks any receptors that have been activated by T/DHT from entering the nucleus.
     
  3. Enzalutamide stops any activated AR, that have managed to get into the nucleus, from instructing DNA to make protein that the cell needs to replicate or metastasise.
Through all of these actions, enzalutamide helps prevent the growth and progression of prostate cancer.
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ari comes in mobile
REFERENCES:
  1. Hormone Health Network. Testosterone and androgens. Available at: https://www.hormone.org/your-health-and-hormones/glands-and-hormones-a-to-z/hormones/testosterone. Accessed October 2025.
  2. NIH. AR Gene. Available at: https://ghr.nlm.nih.gov/gene/AR. Accessed October 2025.
  3. Michaud JE, et al. Testosterone and prostate cancer: An evidence-based review of pathogenesis and oncologic risk. Ther Adv Urol, 2015;7(6):378-387.
  4. Healthline.com. The effects of testosterone on the body. Available at:https://www.healthline.com/health/low-testosterone/effects-on-body#1. Accessed October 2025.
  5. Davey A and Grossmann M. Androgen Receptor Structure, Function and Biology: From Bench to Bedside. Clin Biochem Rev. 2016;37(1):3-15.
  6. National Cancer Institute. NCI Dictionary of Cancer Terms. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/androgen-deprivation
  7. NHS. Treatment Prostate Cancer. Available at: https://www.nhs.uk/conditions/prostate-cancer/treatment/. Accessed October 2025.
  8. Crawford ED, et al. Androgen-targeted therapy in men with prostate cancer: evolving practice and future considerations. Prostate Cancer Prostatic Dis. 2019;22(1):24-38.
  9. Watts EL, et al. Hormone-related diseases and prostate cancer: An English national record linkage study. Int J Cancer 2019, available at: https://onlinelibrary.wiley.com/doi/epdf/10.1002/ijc.32808. Accessed October 2025.
  10. Robins DM, et al. Androgen Receptor Variants and Prostate Cancer in Humanized AR Mice. J Steroid Biochem Mol Biol, 2008;108(3-5):230-236.
  11. Rodriguez-Vida A, et al. Enzalutamide for the treatment of metastatic castration resistant prostate cancer. Drug Design Development Therapy, 2015;9:3325-3339.
  12. Enzalutamide film-coated tablets. Summary of Product Characteristics; Astellas Pharma Ltd. GB SPC available at: https://www.medicines.org.uk/emc/product/10318/smpc. Accessed October 2025.
If you would like to know more about your enzalutamide treatment please refer to the leaflet in your box of tablets or click here: Patient Information Leaflet

MAT-GB-ENZ-2026-00044 | July 2026