ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
ErbB2 Signaling Increases Androgen Receptor Expression in Abiraterone-Resistant Prostate Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 48 citations in OpenAlex.
- ERBB2 as a Prognostic Biomarker in Prostate Cancer: Integration of Single-Cell Transcriptomics, Deep Learning, and Immunohistochemical Validation.Biochemical genetics · 2026Article
- Identification of prognostic genes associated with mitochondria and macrophage polarization in prostate adenocarcinoma based on transcriptome and Mendelian randomization analysis.Discover oncology · 2025Article
- Increased ErbB2 Signaling Is an Early Adaptation to Androgen Signaling Inhibition and Persists in Castration-Resistant Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Article
- Article
- Review
- Molecular landscape for risk prediction and personalized therapeutics of castration-resistant prostate cancer: at a glance.Frontiers in endocrinology · 2024Review
- Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.Biomedicines · 2023Review
- Regulation of Kinase Signaling Pathways by α6β4-Integrins and Plectin in Prostate Cancer.Cancers · 2022Review
- Androgen Metabolism and Response in Prostate Cancer Anti-Androgen Therapy Resistance.International journal of molecular sciences · 2022Review
- Article
- Mechanisms of Resistance to Second-Generation Antiandrogen Therapy for Prostate Cancer: Actual Knowledge and Perspectives.Medical sciences (Basel, Switzerland) · 2022Review
- Neoadjuvant hormonal therapy before radical prostatectomy in high-risk prostate cancer.Nature reviews. Urology · 2021Review
- Article
- Opposing transcriptional programs of KLF5 and AR emerge during therapy for advanced prostate cancer.Nature communications · 2021Article
- Phenotypic characterization of two novel cell line models of castration-resistant prostate cancer.The Prostate · 2021Article
- Tumor Microenvironment-Derived NRG1 Promotes Antiandrogen Resistance in Prostate Cancer.Cancer cell · 2020Article
- AR-dependent phosphorylation and phospho-proteome targets in prostate cancer.Endocrine-related cancer · 2020Review
- Overcoming the mechanisms of primary and acquired resistance to new generation hormonal therapies in advanced prostate cancer: focus on androgen receptor independent pathways.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- Targeted lapatinib anti-HER2/ErbB2 therapy resistance in breast cancer: opportunities to overcome a difficult problem.Cancer drug resistance (Alhambra, Calif.) · 2020Review
- LRIG1 is a pleiotropic androgen receptor-regulated feedback tumor suppressor in prostate cancer.Nature communications · 2019Article
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Authors and funding
16 authors at 2 institutions in 1 country.
Funding
Abstract
purposeErbB2 signaling appears to be increased and may enhance androgen receptor (AR) activity in a subset of patients with castration-resistant prostate cancer (CRPC), but agents targeting ErbB2 have not been effective. This study was undertaken to assess ErbB2 activity in abiraterone-resistant prostate cancer and to determine whether it may contribute to AR signaling in these tumors. EXPERIMENTAL
designAR activity and ErbB2 signaling were examined in the radical prostatectomy specimens from a neoadjuvant clinical trial of leuprolide plus abiraterone and in the specimens from abiraterone-resistant CRPC xenograft models. The effect of ErbB2 signaling on AR activity was determined in two CRPC cell lines. Moreover, the effect of combination treatment with abiraterone and an ErbB2 inhibitor was assessed in a CRPC xenograft model.
resultsWe found that ErbB2 signaling was elevated in residual tumor following abiraterone treatment in a subset of patients and was associated with higher nuclear AR expression. In xenograft models, we similarly demonstrated that ErbB2 signaling was increased and associated with AR reactivation in abiraterone-resistant tumors. Mechanistically, we show that ErbB2 signaling and subsequent activation of the PI3K/AKT signaling stabilizes AR protein. Furthermore, concomitantly treating CRPC cells with abiraterone and an ErbB2 inhibitor, lapatinib, blocked AR reactivation and suppressed tumor progression.
conclusionsErbB2 signaling is elevated in a subset of patients with abiraterone-resistant prostate cancer and stabilizes AR protein. Combination therapy with abiraterone and ErbB2 antagonists may be effective for treating the subset of CRPC with elevated ErbB2 activity. Clin Cancer Res; 22(14); 3672-82. ©2016 AACR.
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