Related Experiment Video

Updated: Feb 26, 2026

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts
09:43

Isolation, Culture, and Characterization of Prostate Cancer-Associated Fibroblasts

Published on: August 1, 2025

860

Alterations in AR-FOXA1 signaling in prostate cancer progression and therapeutic resistance

Shuai Gao1,2, Nolan D Patten3,4, Changmeng Cai3,4

  • 1Department of Cell Biology and Anatomy, New York Medical College, Valhalla, United States.

Journal of the National Cancer Center
|February 25, 2026
PubMed

Insights

Prostate cancer progression involves the androgen receptor (AR) and FOXA1. This review details how changes in the AR-FOXA1 axis drive resistance to treatments like androgen deprivation therapy (ADT) and AR signaling inhibitors (ARSi).

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Androgen receptor (AR) signaling is crucial for prostate cancer (PCa) development and drives resistance to androgen deprivation therapy (ADT).
  • Castration-resistant prostate cancer (CRPC) often involves reactivated AR signaling, despite initial treatment with ADT and next-generation AR signaling inhibitors (ARSi).
  • The pioneer transcription factor FOXA1 is a key regulator of AR activity and is essential for prostate adenocarcinoma development.

Purpose of the Study:

  • To review the alterations in the AR-FOXA1 axis in prostate cancer.
  • To highlight how these changes contribute to treatment resistance.
  • To provide insights into the mechanisms of castration-resistant prostate cancer (CRPC) development.

Main Methods:

  • This is a review article, synthesizing existing research.
  • Focuses on genetic, epigenetic, transcriptional, and posttranscriptional modifications.
  • Examines the AR-FOXA1 axis in the context of ADT and ARSi treatment resistance.

Main Results:

  • The AR-FOXA1 axis undergoes significant alterations in CRPC and in tumors resistant to ARSi.
  • These changes involve genetic, epigenetic, transcriptional, and posttranscriptional modifications.
  • Most CRPC cases regain AR function through various mechanisms impacting the AR-FOXA1 axis.

Conclusions:

  • The AR-FOXA1 axis is a critical factor in prostate cancer progression and the development of treatment resistance.
  • Understanding these alterations is key to developing more effective therapies for advanced prostate cancer.
  • Targeting the AR-FOXA1 axis may offer new therapeutic strategies for CRPC.
Keywords:
Androgen receptorCastration-resistant prostate cancerFOXA1Prostate cancerTranscriptional reprogramming

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