ArticleOncotarget2017
A preclinical evaluation of the MEK inhibitor refametinib in HER2-positive breast cancer cell lines including those with acquired resistance to trastuzumab or lapatinib.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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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
15 citing papers in PubMed, 22 citations in OpenAlex.
- System analysis links SMARCD3 regulons to growth signaling and MEK inhibitor response in everolimus-resistant ER+ breast cancer cells.Cell reports. Medicine · 2025Article
- sTPLS: identifying common and specific correlated patterns under multiple biological conditions.Briefings in bioinformatics · 2025Article
- HER2-Positive Gastric Cancer and Antibody Treatment: State of the Art and Future Developments.Cancers · 2024Review
- Article
- Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer.Cancer biology & therapy · 2023Article
- Clinical Genetic Features and Neoadjuvant Chemotherapy Response in HER2-Low Breast Cancers: A Retrospective, Multicenter Cohort Study.Annals of surgical oncology · 2023Article
- Safety and Clinical Activity of SHR7390 Monotherapy or Combined With Camrelizumab for Advanced Solid Tumor: Results From Two Phase I Trials.The oncologist · 2023Article
- Systemic Therapy for HER2-Positive Metastatic Breast Cancer: Current and Future Trends.Cancers · 2022Review
- Targeting the PI3K and MAPK pathways to improve response to HER2-targeted therapies in HER2-positive gastric cancer.Journal of translational medicine · 2021Article
- Chemoresistance in breast cancer: PI3K/Akt pathway inhibitors vs the current chemotherapy.American journal of cancer research · 2021Review
- Targeting c-Met in triple negative breast cancer: preclinical studies using the c-Met inhibitor, Cpd A.Investigational new drugs · 2020Article
- Combined targeting EGFR and SRC as a potential novel therapeutic approach for the treatment of triple negative breast cancer.Therapeutic advances in medical oncology · 2020Article
- Clinical Pharmacokinetic and Pharmacodynamic Considerations in the (Modern) Treatment of Melanoma.Clinical pharmacokinetics · 2019Review
- Article
- The concomitant use of lapatinib and paracetamol - the risk of interaction.Investigational new drugs · 2018Article
Corrections and comments
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Authors and funding
14 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThe MEK/MAPK pathway is commonly activated in HER2-positive breast cancer, but little investigation of targeting this pathway has been undertaken. Here we present the results of an
methodsA panel of HER2-positive breast cancer cells were profiled for mutational status and also for anti-proliferative response to refametinib alone and in combination with the PI3K inhibitor (PI3Ki) copanlisib and the HER2-targeted therapies trastuzumab and lapatinib. Reverse phase protein array (RPPA) was used to determine the effect of refametinib alone and in combination with PI3Ki and HER2-inhibitors on expression and phosphorylation of proteins in the PI3K/AKT and MEK/MAPK pathways. We validated our proteomic
resultsRefametinib has anti-proliferative effects when used alone in 2/3 parental HER2-positive breast cancer cell lines (HCC1954, BT474), along with 3 models of these 2 cell lines with acquired trastuzumab or lapatinib resistance (6 cell lines tested). Refametinib treatment led to complete inhibition of MAPK signalling. In HCC1954, the most refametinib-sensitive cell line (IC
conclusionRefametinib alone or in combination with copanlisib or lapatinib could represent an improved treatment strategy for some patients with HER2-positive breast cancer, and should be considered for clinical trial evaluation. The direct down-regulation of MEK/MAPK but not AKT signalling by HER2 inhibition (e.g. by lapatinib or trastuzumab), which we demonstrate occurs in 18% of HER2-positive breast cancers may serve as a potential biomarker of responsiveness to the MEK inhibitor refametinib.
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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.