ArticleJournal of the National Cancer Institute2014
Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy.
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Article in Journal of the National Cancer Institute, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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38citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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Who cites it
38 citing papers in PubMed, 54 citations in OpenAlex.
- Trial
- Right-sizing treatment for HER2-positive breast cancer: evolving algorithms across the disease continuum.Nature reviews. Clinical oncology · 2026Review
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- A degrader of HER2 and EGFR abolishes p95HER2 and shows robust antitumor efficacy in HER2-positive breast cancer.Scientific reports · 2026Article
- EMP3 Expression in HER2-Enriched Breast Cancer is Linked to PI3K/AKT Signaling and Indicates Poor Prognosis.Genetics research · 2026Article
- PAK5 promotes the trastuzumab resistance by increasing HER2 nuclear accumulation in HER2-positive breast cancer.Cell death & disease · 2025Article
- Evidence for cytoprotective autophagy in response to HER2-targeted monoclonal antibodies.The Journal of pharmacology and experimental therapeutics · 2025Review
- Targeting RTKs/nRTKs as promising therapeutic strategies for the treatment of triple-negative breast cancer: evidence from clinical trials.Military Medical Research · 2024Review
- Generation of chimeric antigen receptor T cells targeting p95HER2 in solid tumors.Nature communications · 2024Article
- Peptidylarginine deiminase 3 modulates response to neratinib in HER2 positive breast cancer.Oncogenesis · 2024Article
- Resistance mechanisms and prospects of trastuzumab.Frontiers in oncology · 2024Review
- Individualizing Curative-Intent Therapy in HER2-Positive Early-Stage Breast Cancer.Current treatment options in oncology · 2023Review
- Article
- Therapy-Induced Senescence Enhances the Efficacy of HER2-Targeted Antibody-Drug Conjugates in Breast Cancer.Cancer research · 2022Article
- Development of a High-Affinity Antibody against the Tumor-Specific and Hyperactive 611-p95HER2 Isoform.Cancers · 2022Article
- Predictive biomarkers for molecularly targeted therapies and immunotherapies in breast cancer.Archives of pharmacal research · 2022Review
- Review
- Trastuzumab resistance in HER2-positive breast cancer: Mechanisms, emerging biomarkers and targeting agents.Frontiers in oncology · 2022Review
- Review
- RANK signaling increases after anti-HER2 therapy contributing to the emergence of resistance in HER2-positive breast cancer.Breast cancer research : BCR · 2021Article
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Authors and funding
17 authors at 6 institutions in 4 countries.
Josep Lluís Parra-Palau*Authors contributed equally to this work.
Beatriz Morancho*Authors contributed equally to this work.
Vicente Peg*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Marta Escorihuela*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Maurizio Scaltriti*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Rocio Vicario*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Mariano Zacarias-Fluck*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Kim Pedersen*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Atanasio Pandiella*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Paolo Nuciforo*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Violeta Serra*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Javier Cortés*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
José Baselga*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Charles M Perou*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Aleix Prat*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Isabel T Rubio*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Joaquín Arribas*Authors contributed equally to this work.Affiliations of authors: Preclinical Research (JLPP, BM, ME, RV, MZF, KP, VS, AP, JA) and Clinical Research Programs (PN, JC, ITR), Vall d'Hebron Institute of Oncology (VHIO), Barcelona, Spain; Pathology Department, Vall d'Hebron University Hospital, Barcelona, Spain (VP); Human Oncology and Pathogenesis Program (HOPP) and Memorial Sloan Kettering Cancer Center, New York, NY (MS, JB); Instituto de Biología Molecular y Celular del Cáncer, Campus Miguel de Unamuno, Salamanca, Spain (AP); Lineberger Comprehensive Cancer Center, Chapel Hill, NC (CMP); Department of Biochemistry and Molecular Biology, Universitat Autonoma de Barcelona, Campus de la UAB, Bellaterra, Spain (JA); Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain (JA).
Universitat Autònoma de Barcelona · ESMemorial Sloan Kettering Cancer Center · USGeneral Department of Preventive Medicine · VNHebron University · PSVall d'Hebron Institut de Recerca · ESVall d'Hebron Institute of Oncology
Funding
Tissue Procurement & PathologyP50CA058223 · NCI · UNIV OF NORTH CAROLINA CHAPEL HILL · PI KATHERINE A. HOADLEY · 1992 to 2026
$59.3MNCI NIH HHS P50 CA058223NCI NIH HHS P50-CA58223-09A1
Abstract
Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are currently treated with trastuzumab, an anti-HER2 antibody. About 30% of these tumors express a group of HER2 fragments collectively known as p95HER2. Our previous work indicated that p95HER2-positive tumors are resistant to trastuzumab monotherapy. However, recent results showed that tumors expressing the most active of these fragments, p95HER2/611CTF, respond to trastuzumab plus chemotherapy. To clarify this discrepancy, we analyzed the response to chemotherapy of cell lines transfected with p95HER2/611CTF and patient-derived xenografts (n = 7 mice per group) with different levels of the fragment. All statistical tests were two-sided. p95HER2/611CTF-negative and positive tumors showed different responses to various chemotherapeutic agents, which are particularly effective on p95HER2/611CTF-positive cells. Furthermore, chemotherapy sensitizes p95HER2/611CTF-positive patient-derived xenograft tumors to trastuzumab (mean tumor volume, trastuzumab alone: 906 mm(3), 95% confidence interval = 1274 to 538 mm(3); trastuzumab+doxorubicin: 259 mm(3), 95% confidence interval = 387 to 131 mm(3); P < .001). This sensitization may be related to HER2 stabilization induced by chemotherapy in p95HER2/611CTF-positive cells.
Indexed as
AnimalsAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic AgentsAntineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsCell ProliferationDoxorubicinErb-b2 Receptor Tyrosine KinasesFemaleFlow CytometryGene Expression ProfilingHumansImmunohistochemistryMiceMicroscopy, ConfocalAnthracyclinesAntibodies, Monoclonal, HumanizedAntineoplastic AgentsDoxorubicinERBB2 protein, humanErbb2 protein, mouseErb-b2 Receptor Tyrosine KinasesTaxoidsTrastuzumab
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