ArticleNeoplasia (New York, N.Y.)2013
Inhibition of the growth of patient-derived pancreatic cancer xenografts with the MEK inhibitor trametinib is augmented by combined treatment with the epidermal growth factor receptor/HER2 inhibitor lapatinib.
Article in Neoplasia (New York, N.Y.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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Who cites it
51 citing papers in PubMed, 86 citations in OpenAlex.
- A Multicenter, Open-Label Phase II Clinical Trial of Combined MEK plus EGFR Inhibition for Chemotherapy-Refractory Advanced Pancreatic Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Reactivation of DRP1 plays a functional role in resistance to MEK inhibition in pancreatic cancer cells.British journal of cancer · 2026Article
- Reactivation of DRP1 plays a functional role in resistance to MEK inhibition in pancreatic cancer cells.bioRxiv : the preprint server for biology · 2026Article
- EC359 Enhances Trametinib Efficacy inBiomolecules · 2025Article
- Cellular and molecular mechanisms of arenobufagin in cancer therapy: a systematic review.Discover oncology · 2025Review
- Advances in Small-molecule Dual Inhibitors Targeting EGFR and HER2 Receptors as Anti-cancer Agents.Current medicinal chemistry · 2025Review
- Pancreatic cancer acquires resistance to MAPK pathway inhibition by clonal expansion and adaptive DNA hypermethylation.Clinical epigenetics · 2024Article
- Activation of the EGFR/PI3K/AKT pathway limits the efficacy of trametinib treatment in head and neck cancer.Molecular oncology · 2023Article
- Targeting KRAS for the potential treatment of pancreatic ductal adenocarcinoma: Recent advancements provide hope (Review).Oncology reports · 2023Review
- Epigenomic and transcriptomic landscaping unraveled candidate repositioned therapeutics for non-functioning pituitary neuroendocrine tumors.Journal of endocrinological investigation · 2023Article
- Automated biophysical classification of apoptotic pancreatic cancer cell subpopulations by using machine learning approaches with impedance cytometry.Lab on a chip · 2022Article
- Apoptotic Bodies in the Pancreatic Tumor Cell Culture Media Enable Label-Free Drug Sensitivity Assessment by Impedance Cytometry.Advanced biology · 2021Article
- Mimicking and surpassing the xenograft model with cancer-on-chip technology.EBioMedicine · 2021Review
- Evidence of Omics, Immune Infiltration, and Pharmacogenomic for SENP1 in the Pan-Cancer Cohort.Frontiers in pharmacology · 2021Article
- Constitutive Activation of RAS/MAPK Pathway Cooperates with Trisomy 21 and Is Therapeutically Exploitable in Down Syndrome B-cell Leukemia.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Article
- Electrophysiology-based stratification of pancreatic tumorigenicity by label-free single-cell impedance cytometry.Analytica chimica acta · 2020Article
- MiRNA-Mediated Subpathway Identification and Network Module Analysis to Reveal Prognostic Markers in Human Pancreatic Cancer.Frontiers in genetics · 2020Article
- Generation and application of patient-derived xenograft models in pancreatic cancer research.Chinese medical journal · 2019Review
- Identification of Resistance Pathways Specific to Malignancy Using Organoid Models of Pancreatic Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2019Article
- Co-dependency between KRAS addiction and ARHGEF2 promotes an adaptive escape from MAPK pathway inhibition.Small GTPases · 2019Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations of the oncogene KRAS are important drivers of pancreatic cancer progression. Activation of epidermal growth factor receptor (EGFR) and human EGFR2 (HER2) is observed frequent in pancreatic adenocarcinomas. Because of co-activation of these two signaling pathways, we assessed the efficacy of inhibition of EGFR/HER2 receptors and the downstream KRAS effector, mitogen-activated protein kinase/extracellular-signal regulated kinase (ERK) kinase 1 and 2 (MEK1/2), on pancreatic cancer proliferation in vitro and in a murine orthotopic xenograft model. Treatment of established and patient-derived pancreatic cancer cell lines with the MEK1/2 inhibitor trametinib (GSK1120212) inhibited proliferation, and addition of the EGFR/HER2 inhibitor lapatinib enhanced the inhibition elicited by trametinib in three of eight cell lines. Importantly, in the orthotopic xenograft model, treatment with lapatinib and trametinib resulted in significantly enhanced inhibition of tumor growth relative to trametinib treatment alone in four of five patient-derived tumors tested and was, in all cases, significantly more effective in reducing the size of established tumors than treatment with lapatinib or trametinib alone. Acute treatment of established tumors with trametinib resulted in an increase in AKT2 phosphorylation that was blunted in mice treated with both trametinib and lapatinib. These data indicate that inhibition of the EGFR family receptor signaling may contribute to the effectiveness of MEK1/2 inhibition of tumor growth possibly through the inhibition of feedback activation of receptor tyrosine kinases in response to inhibition of the RAS-RAF-MEK-ERK pathway. These studies provide a rationale for assessing the co-inhibition of these pathways in the treatment of pancreatic cancer patients.
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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.