ArticleMolecular cancer therapeutics2013
Subtype-specific MEK-PI3 kinase feedback as a therapeutic target in pancreatic adenocarcinoma.
Article in Molecular cancer therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 37 citations in OpenAlex.
- Effect of Selumetinib and MK-2206 vs Oxaliplatin and Fluorouracil in Patients With Metastatic Pancreatic Cancer After Prior Therapy: SWOG S1115 Study Randomized Clinical Trial.JAMA oncology · 2017Trial
- 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
- Review
- Evaluation of the Cytotoxic and Antimigratory Activity Induced by [Pt(1-hexyl-1International journal of molecular sciences · 2026Article
- Different Cytotoxic Effects of Cisplatin on Pancreatic Ductal Adenocarcinoma Cell Lines.International journal of molecular sciences · 2024Article
- Targeting Non-V600 Mutations in BRAF: A Single Institution Retrospective Analysis and Review of the Literature.Drugs in R&D · 2024Review
- Recent advances in targeted therapy for pancreatic adenocarcinoma.World journal of gastrointestinal oncology · 2023Review
- High-Throughput Functional Evaluation of MAP2K1 Variants in Cancer.Molecular cancer therapeutics · 2023Article
- KRAS Mutation Variants and Co-occurring PI3K Pathway Alterations Impact Survival for Patients with Pancreatic Ductal Adenocarcinomas.The oncologist · 2022Article
- Review
- Hacking Pancreatic Cancer: Present and Future of Personalized Medicine.Pharmaceuticals (Basel, Switzerland) · 2021Review
- Modeling Adaptive Resistance of KRAS Mutant Colorectal Cancer to MAPK Pathway Inhibitors with a Three-Dimensional Tumor Model.ACS pharmacology & translational science · 2020Article
- Developing effective combination therapy for pancreatic cancer: An overview.Pharmacological research · 2020Review
- Preclinical Modelling of PDA: Is Organoid the New Black?International journal of molecular sciences · 2019Review
- Cyclical Treatment of Colorectal Tumor Spheroids Induces Resistance to MEK Inhibitors.Translational oncology · 2019Article
- New Horizons in the Treatment of Metastatic Pancreatic Cancer: A Review of the Key Biology Features and the Most Recent Advances to Treat Metastatic Pancreatic Cancer.Targeted oncology · 2018Review
- Epithelial-mesenchymal-transition-inducing transcription factors: new targets for tackling chemoresistance in cancer?Oncogene · 2018Review
- Deciphering the link between PI3K and PAK: An opportunity to target key pathways in pancreatic cancer?Oncotarget · 2017Review
- Article
- Molecular therapeutics in pancreas cancer.World journal of gastrointestinal oncology · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Mutations in the KRAS oncogene are dominant features in pancreatic ductal adenocarcinoma (PDA). Because KRAS itself is considered "undruggable," targeting pathways downstream of KRAS are being explored as a rational therapeutic strategy. We investigated the consequences of MAP-ERK kinase (MEK) inhibition in a large PDA cell line panel. Inhibition of MEK activated phosphoinositide 3-kinase in an EGF receptor (EGFR)-dependent fashion and combinations of MEK and EGFR inhibitors synergistically induced apoptosis. This combinatorial effect was observed in the epithelial but not mesenchymal subtype of PDA. RNA expression analysis revealed predictors of susceptibility to the combination, including E-cadherin, HER3, and the miR200-family of microRNAs, whereas expression of the transcription factor ZEB1 was associated with resistance to the drug combination. Knockdown of HER3 in epithelial-type and ZEB1 in mesenchymal-type PDA cell lines resulted in sensitization to the combination of MEK and EGFR inhibitors. Thus, our findings suggest a new, subtype-specific, and personalized therapeutic strategy for pancreatic cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.