ArticleClinical cancer research : an official journal of the American Association for Cancer Research2011
Reduced dose and intermittent treatment with lapatinib and trastuzumab for potent blockade of the HER pathway in HER2/neu-overexpressing breast tumor xenografts.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
What it found
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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
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 86 citations in OpenAlex.
- Risk of severe diarrhea with dual anti-HER2 therapies: a meta-analysis.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2014Pooled it
- Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer.Breast cancer research and treatment · 2018Trial
- Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- Comparison of Cell Line-Derived and Patient-Derived Xenograft Technologies in Oncology (Review).Bulletin of experimental biology and medicine · 2026Review
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- Depicting Biomarkers for HER2-Inhibitor Resistance: Implication for Therapy in HER2-Positive Breast Cancer.Cancers · 2024Review
- Antibody dependent cell-mediated cytotoxicity selection pressure induces diverse mechanisms of resistance.Cancer biology & therapy · 2023Article
- A Multiparameter Molecular Classifier to Predict Response to Neoadjuvant Lapatinib plus Trastuzumab without Chemotherapy in HER2+ Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Estrogen/HER2 receptor crosstalk in breast cancer: combination therapies to improve outcomes for patients with hormone receptor-positive/HER2-positive breast cancer.NPJ breast cancer · 2023Review
- The oncogenic roles and clinical implications of YAP/TAZ in breast cancer.British journal of cancer · 2023Review
- Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models.NPJ breast cancer · 2021Article
- Immunotherapy for Breast Cancer Treatment.Iranian biomedical journal · 2021Article
- Article
- Laboratory Models for Investigating Breast Cancer Therapy Resistance and Metastasis.Frontiers in oncology · 2021Review
- Article
- Towards personalized treatment for early stage HER2-positive breast cancer.Nature reviews. Clinical oncology · 2020Review
- DE-ESCALATING TREATMENT FOR HER2-POSITIVE EARLY BREAST CANCER.Transactions of the American Clinical and Climatological Association · 2020Article
- Targeting the Mevalonate Pathway to Overcome Acquired Anti-HER2 Treatment Resistance in Breast Cancer.Molecular cancer research : MCR · 2019Article
- A combinatorial biomarker predicts pathologic complete response to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2+ breast cancer.Annals of oncology : official journal of the European Society for Medical Oncology · 2019Article
- Cyclical Treatment of Colorectal Tumor Spheroids Induces Resistance to MEK Inhibitors.Translational oncology · 2019Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 1 country.
Funding
Abstract
purposeWe have shown that incomplete blockade of the human epidermal growth factor (HER) pathway is a mechanism of resistance to treatment with trastuzumab (T) in HER2-overexpressing tumor xenografts. We now investigate whether the addition of lapatinib (L), a dual HER1/2 kinase inhibitor, to T results in more potent inhibition of the pathway and therefore inhibition of tumor growth, and whether reduced dose and intermittent treatment with the combination is equally effective. EXPERIMENTAL
designNude mice bearing HER2-overexpressing MCF7/HER2-18 or BT-474 xenograft tumors were treated with L and T, alone or in various combinations with other HER inhibitors. L + T for short duration (14 and 42 days), intermittent administration (14 days on/off), and reduced dosing (half dose) was also investigated. Inhibition of tumor growth, downstream signaling, proliferation, and induction of apoptosis were assessed. All statistical tests were two-sided.
resultsL + T was the most effective regimen in both MCF7/HER2-18 and BT-474 xenografts with complete regression (CR) of tumor observed in all mice. Intermittent and reduced dose treatment (½ dose) resulted in high rates of CR and low rates of tumor recurrence that were comparable to full dose continuous treatment. L + T resulted in significantly reduced downstream signaling and proliferation, and increased apoptosis.
conclusionsL + T is a potent and effective combination even when given in reduced dose or intermittent schedule potentially resulting in lower toxicity and reduced cost if translated to patients. These findings warrant timely clinical testing.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.