ArticleBritish journal of cancer2019
Dacomitinib, but not lapatinib, suppressed progression in castration-resistant prostate cancer models by preventing HER2 increase.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 23 citations in OpenAlex.
- HER2 as a molecular trojan horse in prostate cancer: mechanistic insights and therapeutic unlocks.Molecular biology reports · 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
- Prognostic and Predictive Roles of HER2 Status in Non-Breast and Non-Gastroesophageal Carcinomas.Cancers · 2024Review
- Amiloride Sensitizes Prostate Cancer Cells to the Reversible Tyrosine Kinase Inhibitor Lapatinib by Modulating ERBB3 Subcellular Localization.Research square · 2024Article
- Development of new TAK-285 derivatives as potent EGFR/HER2 inhibitors possessing antiproliferative effects against 22RV1 and PC3 prostate carcinoma cell lines.Journal of enzyme inhibition and medicinal chemistry · 2023Article
- Prostate cancer and bone: clinical presentation and molecular mechanisms.Endocrine-related cancer · 2023Review
- Cisplatin-induced increase in heregulin 1 and its attenuation by the monoclonal ErbB3 antibody seribantumab in bladder cancer.Scientific reports · 2023Article
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- Article
- Choosing Kinase Inhibitors for Androgen Deprivation Therapy-Resistant Prostate Cancer.Pharmaceutics · 2022Review
- CMTM5 inhibits the development of prostate cancer via the EGFR/PI3K/AKT signaling pathway.Molecular medicine reports · 2022Article
- Article
- The influence of testosterone suppression on HER2 immunoexpression in prostatic neoplastic tissue.Molecular and clinical oncology · 2021Article
- Review
- KIF15 Promotes Progression of Castration Resistant Prostate Cancer by Activating EGFR Signaling Pathway.Frontiers in oncology · 2021Article
- A Mansonone Derivative Coupled with Monoclonal Antibody 4D5-Modified Chitosan Inhibit AKR1C3 to Treat Castration-Resistant Prostate Cancer.International journal of nanomedicine · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundDespite overexpression of the ErbB (EGFR/HER2/ErbB3/ErbB4) family in castration-resistant prostate cancer (CRPC), some inhibitors of this family, including the dual EGFR/HER2 inhibitor lapatinib, failed in Phase II clinical trials. Hence, we investigated mechanisms of lapatinib resistance to determine whether alternate ErbB inhibitors can succeed.
methodsThe CWR22 human tumour xenograft and its CRPC subline 22Rv1 and sera from lapatinib-treated CRPC patients from a previously reported Phase II trial were used to study lapatinib resistance. Mechanistic studies were conducted in LNCaP, C4-2 and 22Rv1 cell lines.
resultsLapatinib increased intratumoral HER2 protein, which encouraged resistance to this treatment in mouse models. Sera from CRPC patients following lapatinib treatment demonstrated increased HER2 levels. Investigation of the mechanism of lapatinib-induced HER2 increase revealed that lapatinib promotes HER2 protein stability, leading to membrane localisation, EGFR/HER2 heterodimerisation and signalling, elevating cell viability. Knockdown of HER2 and ErbB3, but not EGFR, sensitised CRPC cells to lapatinib. At equimolar concentrations, the recently FDA-approved pan-ErbB inhibitor dacomitinib decreased HER2 protein stability, prevented ErbB membrane localisation (despite continued membrane integrity) and EGFR/HER2 heterodimerisation, thereby decreasing downstream signalling and increasing apoptosis.
conclusionsTargeting the EGFR axis using the irreversible pan-ErbB inhibitor dacomitinib is a viable therapeutic option for CRPC.
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