ArticleOncotarget2015
Inhibition of the HER2-YB1-AR axis with Lapatinib synergistically enhances Enzalutamide anti-tumor efficacy in castration resistant prostate cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 44 citations in OpenAlex.
- Phase II Study of Enzalutamide for Patients With Androgen Receptor-Positive Salivary Gland Cancers (Alliance A091404).Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2022Trial
- Repurposing of lansoprazole and nitazoxanide as NR2F2 inhibitors in the gastric cancer cell line GCIY: computational insights and siRNA-mediatedFrontiers in chemistry · 2026Article
- Identification of prognostic genes associated with mitochondria and macrophage polarization in prostate adenocarcinoma based on transcriptome and Mendelian randomization analysis.Discover oncology · 2025Article
- Novel hormone therapies for advanced prostate cancer: Understanding and countering drug resistance.Journal of pharmaceutical analysis · 2025Review
- Amiloride sensitizes prostate cancer cells to the reversible tyrosine kinase inhibitor lapatinib by modulating Erbb3 subcellular localization.Cellular and molecular life sciences : CMLS · 2024Article
- The extent of androgen receptor and HER2 expression allows for targeted therapy in most cases of salivary duct carcinoma: analysis of clinical and histopathological data in a tertiary care center.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2024Article
- Anti-tumour effects of lapatinib on HER2-positive canine prostatic carcinoma cell lines.Open veterinary journal · 2024Article
- Basal epithelial cells in prostate development, tumorigenesis, and cancer progression.Cell cycle (Georgetown, Tex.) · 2023Review
- Strategies to Re-Sensitize Castration-Resistant Prostate Cancer to Antiandrogen Therapy.Biomedicines · 2023Review
- Article
- 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
- A comprehensive review of the functions of YB-1 in cancer stemness, metastasis and drug resistance.Cellular signalling · 2021Review
- Hydralazine and Enzalutamide: Synergistic Partners against Prostate Cancer.Biomedicines · 2021Article
- Construction of enzalutamide-resistant cell model of prostate cancer and preliminary screening of potential drug-resistant genes.Experimental biology and medicine (Maywood, N.J.) · 2021Article
- Review
- Overexpression of CXCR7 is a Novel Indicator for Enzalutamide Resistance in Castration-Resistant Prostate Cancer Patients.Disease markers · 2021Article
- 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
- Dacomitinib, but not lapatinib, suppressed progression in castration-resistant prostate cancer models by preventing HER2 increase.British journal of cancer · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Incurable castration-resistant prostate cancer (CRPC) is driven by androgen receptor (AR) activation. Potent therapies that prevent AR signaling, such as Enzalutamide (ENZ), are mainstay treatments for CRPC; however patients eventually progress with ENZ resistant (ENZR) disease. In this study, we investigated one mechanism of ENZ resistance, and tried to improve therapeutic efficiency of ENZ. We found HER2 expression is increased in ENZR tumors and cell lines, and is induced by ENZ treatment of LNCaP cells. ENZ-induced HER2 overexpression was dependent on AKT-YB1 activation and modulated AR activity. HER2 dependent AR activation in LNCaP and ENZR cells was effectively blocked by treatment with the EGFR/HER2 inhibitor Lapatinib, which reduced cell viability and increased apoptosis. Despite efficacy in vitro, in vivo monotherapy with Lapatinib did not prevent ENZR tumor growth. However, combination treatment of Lapatinib with ENZ most effectively induced cell death in LNCaP cells in vitro and was more effective than ENZ alone in preventing tumor growth in an in vivo model of CRPC. These results suggest that while HER2 overexpression and subsequent AR activation is a targetable mechanism of resistance to ENZ, therapy using Lapatinib is only a rational therapeutic approach when used in combination with ENZ in CRPC.
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