ArticleNeoplasia (New York, N.Y.)2014
Co-treatment with panitumumab and trastuzumab augments response to the MEK inhibitor trametinib in a patient-derived xenograft model of pancreatic cancer.
Article in Neoplasia (New York, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 36 citations in OpenAlex.
- PRMT5 Identified as a Viable Target for Combination Therapy in Preclinical Models of Pancreatic Cancer.Biomolecules · 2025Article
- Dual anti-HER2/EGFR inhibition synergistically increases therapeutic effects and alters tumor oxygenation in HNSCC.Scientific reports · 2024Article
- The EGFR-HSF1 axis accelerates the tumorigenesis of pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2021Article
- Retrospective Case Series Analysis ofJCO precision oncology · 2021Article
- Targeted CRISPR screening identifies PRMT5 as synthetic lethality combinatorial target with gemcitabine in pancreatic cancer cells.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- CRISPR knockout screening identifies combinatorial drug targets in pancreatic cancer and models cellular drug response.Nature communications · 2018Article
- Biomarker-Based Therapy in Pancreatic Ductal Adenocarcinoma: An Emerging Reality?Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Review
- Inhibition of the MEK/ERK pathway augments nab-paclitaxel-based chemotherapy effects in preclinical models of pancreatic cancer.Oncotarget · 2018Article
- Dysbindin promotes progression of pancreatic ductal adenocarcinoma via direct activation of PI3K.Journal of molecular cell biology · 2017Article
- Cucurbitacin B and SCH772984 exhibit synergistic anti-pancreatic cancer activities by suppressing EGFR, PI3K/Akt/mTOR, STAT3 and ERK signaling.Oncotarget · 2017Article
- Pancreatic Cancer: Molecular Characterization, Clonal Evolution and Cancer Stem Cells.Biomedicines · 2017Review
- MEK inhibitors induce Akt activation and drug resistance by suppressing negative feedback ERK-mediated HER2 phosphorylation at Thr701.Molecular oncology · 2017Article
- Frequent co-expression of EGFR and NeuGcGM3 ganglioside in cancer: it's potential therapeutic implications.Clinical & experimental metastasis · 2016Article
- Adjuvant Trametinib Delays the Outgrowth of Occult Pancreatic Cancer in a Mouse Model of Patient-Derived Liver Metastasis.Annals of surgical oncology · 2016Article
- Molecular targets for the treatment of pancreatic cancer: Clinical and experimental studies.World journal of gastroenterology · 2016Review
- Biomarkers and Targeted Therapy in Pancreatic Cancer.Biomarkers in cancer · 2016Review
- Patient-Derived Tumor Xenografts Are Susceptible to Formation of Human Lymphocytic Tumors.Neoplasia (New York, N.Y.) · 2015Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and epidermal growth factor receptor (EGFR) family signaling are drivers of tumorigenesis in pancreatic ductal adenocarcinoma (PDAC). Previous studies have demonstrated that combinatorial treatment of PDAC xenografts with the mitogen-activated protein kinase-extracellular-signal-regulated kinase (ERK) kinase1/2 (MEK1/2) inhibitor trametinib and the dual EGFR/human epidermal growth factor receptor 2 (HER2) inhibitor lapatinib provided more effective inhibition than either treatment alone. In this study, we have used the therapeutic antibodies, panitumumab (specific for EGFR) and trastuzumab (specific for HER2), to probe the role of EGFR and HER2 signaling in the proliferation of patient-derived xenograft (PDX) tumors. We show that dual anti-EGFR and anti-HER2 therapy significantly augmented the growth inhibitory effects of the MEK1/2 inhibitor trametinib in three different PDX tumors. While significant growth inhibition was observed in both KRAS mutant xenograft groups receiving trametinib and dual antibody therapy (tumors 366 and 608), tumor regression was observed in the KRAS wild-type xenografts (tumor 738) treated in the same manner. Dual antibody therapy in conjunction with trametinib was equally or more effective at inhibiting tumor growth and with lower apparent toxicity than trametinib plus lapatinib. Together, these studies provide further support for a role for EGFR and HER2 in pancreatic cancer proliferation and underscore the importance of therapeutic intervention in both the KRAS-rapidly accelerated fibrosarcoma kinase (RAF)-MEK-ERK and EGFR-HER2 pathways to achieve maximal therapeutic efficacy in patients.
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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.