# Androgen receptor pathway inhibitor (ARPI)

Source: https://nuclide.cc/terms/arpi/  
Nuclide record `arpi` (Term). Data CC BY-NC 4.0, attribute "Data from Nuclide (nuclide.cc)"; commercial use needs a licence.

## TL;DR

The newer prostate cancer hormone pills (abiraterone, enzalutamide, apalutamide, darolutamide) that block the androgen receptor or the last steps of androgen production, used on top of standard testosterone suppression.

## Summary

Abiraterone blocks CYP17 androgen synthesis (given with prednisone); enzalutamide, apalutamide and darolutamide are potent AR antagonists. Adding an ARPI to ADT extends survival in metastatic hormone-sensitive disease (LATITUDE, ARCHES, TITAN, ARASENS), in non-metastatic castration-resistant disease and in castration-resistant disease before or after docetaxel. Resistance arises via AR amplification, ligand-binding domain mutations, the AR-V7 splice variant and lineage plasticity to neuroendocrine disease; switching ARPIs after failure gives little benefit, so PSMA radioligands, PARP inhibitors and chemotherapy follow. Older antiandrogens (bicalutamide) are weaker first-generation drugs.

## Fields

- Kind: Term
- Last checked: 2026-09-09
- Also known as: ARPI; ARPIs; ARSI; androgen receptor signalling inhibitor; androgen receptor pathway inhibitor; novel hormonal agent; NHA; next-generation antiandrogen; second-generation antiandrogen; AR antagonist; AR inhibitor; antiandrogen; anti-androgen; AR-V7; AR-targeted; AR antagonists

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/Antiandrogen
- Wikipedia: https://en.wikipedia.org/wiki/Antiandrogen

## Connected records

- indications: [Prostate cancer](https://nuclide.cc/indications/prostate/)
- drugs: [Abiraterone acetate](https://nuclide.cc/drugs/abiraterone/), [Enzalutamide](https://nuclide.cc/drugs/enzalutamide/)
- terms: [mCRPC and mHSPC (castration-resistant vs hormone-sensitive prostate cancer)](https://nuclide.cc/terms/mcrpc-mhspc/)
- pairings: [Radium-223 with abiraterone: a caution, not a combination](https://nuclide.cc/pairings/radium223-abiraterone-caution/)
- key papers: [PSMAfore: 177Lu-PSMA-617 versus a change of androgen receptor pathway inhibitor in taxane-naive mCRPC](https://nuclide.cc/key-papers/paper-psmafore-lancet-2024/)

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