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Updated: Jan 27, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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BAG1L: a promising therapeutic target for androgen receptor-dependent prostate cancer

Irene I Lee1,2, Nane C Kuznik3, Jaice T Rottenberg1,2

  • 1Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.

Journal of Molecular Endocrinology
|March 27, 2019
PubMed

Insights

Targeting the androgen receptor (AR) N-terminus is crucial for advanced prostate cancer. The cochaperone BAG1L shows promise as a therapeutic target for castration-resistant prostate cancer (CRPC) by enhancing AR activity.

Area of Science:

  • Oncology
  • Molecular Biology
  • Endocrinology

Background:

  • Androgens regulate prostate growth, acting via the androgen receptor (AR).
  • Current therapies target the AR ligand-binding domain (LBD), but resistance develops, leading to castration-resistant prostate cancer (CRPC).
  • CRPC involves constitutively active AR splice variants lacking the LBD, necessitating new therapeutic strategies.

Purpose of the Study:

  • To review literature on targeting the AR N-terminus for prostate cancer therapy.
  • To evaluate BAG1L as a potential therapeutic target for AR-positive prostate cancer, particularly CRPC.

Main Methods:

  • Literature review of studies on androgen receptor signaling in prostate cancer.
  • Analysis of the role of AR N-terminal activity and its modulation.
  • Investigation of cochaperone interactions with the AR N-terminus, focusing on BAG1L.

Main Results:

  • The AR N-terminal region is critical for AR signaling, especially in CRPC.
  • Targeting the AR N-terminus is challenging due to its unstructured nature.
  • BAG1L enhances AR activity via the AR Amino-terminal domain (AF1) and is a promising target.

Conclusions:

  • Developing therapies targeting the AR N-terminus is essential for overcoming resistance in advanced prostate cancer.
  • BAG1L represents a viable therapeutic target for inhibiting AR signaling in castration-resistant prostate cancer.
  • Targeting BAG1L offers a novel strategy for treating patients with advanced, treatment-resistant prostate cancer.
Keywords:
cochaperonemolecular chaperonenuclear receptorssignal transductiontranscription

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