Related Experiment Video

Updated: Mar 24, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
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A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer

Published on: March 6, 2018

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ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer

Shuai Gao1, Huihui Ye2, Sean Gerrin2

  • 1Center for Personalized Cancer Therapy, University of Massachusetts Boston, Boston, Massachusetts. Hematology-Oncology Division, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
|March 4, 2016
PubMed
Abstract

Insights

Elevated ErbB2 signaling in castration-resistant prostate cancer (CRPC) reactivates androgen receptor (AR) signaling. Combination therapy targeting both ErbB2 and AR may improve treatment outcomes for patients with abiraterone-resistant CRPC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Cancer Research

Background:

  • Castration-resistant prostate cancer (CRPC) remains a significant clinical challenge.
  • Androgen receptor (AR) signaling is a key driver in prostate cancer progression.
  • ErbB2 signaling is implicated in some CRPC cases, but its role in abiraterone resistance is not fully understood.

Purpose of the Study:

  • To investigate the role of ErbB2 signaling in abiraterone-resistant prostate cancer.
  • To determine if ErbB2 signaling contributes to AR activity in these resistant tumors.
  • To evaluate the efficacy of combination therapy targeting ErbB2 and AR.

Main Methods:

  • Analysis of ErbB2 signaling and AR activity in patient samples from a neoadjuvant clinical trial.
  • Examination of abiraterone-resistant CRPC xenograft models.
  • In vitro studies using CRPC cell lines to assess the effect of ErbB2 on AR activity.
  • In vivo assessment of combination therapy with abiraterone and an ErbB2 inhibitor (lapatinib).

Main Results:

  • ErbB2 signaling was elevated in residual tumors after abiraterone treatment and correlated with increased nuclear AR expression.
  • ErbB2 signaling and AR reactivation were observed in abiraterone-resistant xenograft models.
  • ErbB2 signaling, via PI3K/AKT pathway activation, was found to stabilize AR protein.
  • Combination treatment with abiraterone and lapatinib inhibited AR reactivation and suppressed tumor progression in CRPC models.

Conclusions:

  • Elevated ErbB2 signaling is a feature of a subset of abiraterone-resistant prostate cancers.
  • ErbB2 signaling contributes to AR protein stabilization in these tumors.
  • Combination therapy with abiraterone and ErbB2 inhibitors presents a potential therapeutic strategy for a specific CRPC patient group.

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