ReviewLung cancer (Amsterdam, Netherlands)2014
MEK inhibition in non-small cell lung cancer.
Review in Lung cancer (Amsterdam, Netherlands), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 72 citations in OpenAlex.
- Preclinical and clinical evaluation of futibatinib in combination with binimetinib in patients with advanced cancer.Investigational new drugs · 2026Article
- Chemoresistance Mechanisms in Non-Small Cell Lung Cancer-Opportunities for Drug Repurposing.Applied biochemistry and biotechnology · 2024Review
- Effect of isolated grandivittin from Ferulago trifida Boiss. (Apiaceae) on the proliferation and apoptosis of human lung cancer A549 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Clinical characteristics and outcomes of phase I cancer patients with CCNE1 amplification: MD Anderson experiences.Scientific reports · 2022Review
- The efficacy and safety of selumetinib as secondary therapy for late-stage and metastatic non-small cell lung cancer: results from a systematic review and meta-analysis.Annals of translational medicine · 2022Article
- Phase I Trial of Definitive Concurrent Chemoradiotherapy and Trametinib for KRAS-Mutated Non-Small Cell Lung Cancer.Cancer treatment and research communications · 2022Article
- Selective KRAS G12C inhibitors in non-small cell lung cancer: chemistry, concurrent pathway alterations, and clinical outcomes.NPJ precision oncology · 2021Review
- The improbable targeted therapy: KRAS as an emerging target in non-small cell lung cancer (NSCLC).Cell reports. Medicine · 2021Review
- Advanced NSCLC Patients With EGFR T790M Harboring TP53 R273C or KRAS G12V Cannot Benefit From Osimertinib Based on a Clinical Multicentre Study by Tissue and Liquid Biopsy.Frontiers in oncology · 2021Article
- The Clinical Kinase Index: A Method to Prioritize Understudied Kinases as Drug Targets for the Treatment of Cancer.Cell reports. Medicine · 2020Article
- The Crosstalk between Src and Hippo/YAP Signaling Pathways in Non-Small Cell Lung Cancer (NSCLC).Cancers · 2020Review
- Concurrent inhibition of ErbB family and MEK/ERK kinases to suppress non-small cell lung cancer proliferation.American journal of translational research · 2020Article
- FRA1 contributes to MEK-ERK pathway-dependent PD-L1 upregulation by KRAS mutation in premalignant human bronchial epithelial cells.American journal of translational research · 2020Article
- A novel small-molecule inhibitor of trefoil factor 3 (TFF3) potentiates MEK1/2 inhibition in lung adenocarcinoma.Oncogenesis · 2019Article
- Pulsatile MEK Inhibition Improves Anti-tumor Immunity and T Cell Function in Murine Kras Mutant Lung Cancer.Cell reports · 2019Article
- Integrative analysis reveals distinct subtypes with therapeutic implications in KRAS-mutant lung adenocarcinoma.EBioMedicine · 2018Article
- Outcome analysis of Phase I trial patients with metastaticOncotarget · 2018Article
- Copper Chelation as Targeted Therapy in a Mouse Model of Oncogenic BRAF-Driven Papillary Thyroid Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Review
- Ginsenosides synergize with mitomycin C in combating human non-small cell lung cancer by repressing Rad51-mediated DNA repair.Acta pharmacologica Sinica · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
KRAS mutations are the most common mutations in non-small cell lung cancer (NSCLC) with adenocarcinoma histology. KRAS mutations result in the activation of the RAF-MEK-ERK pathway, and agents that target RAF-MEK-ERK pathways have been investigated in KRAS mutant NSCLC. The two agents furthest in development are selumetinib and trametinib. Trametinib has greater binding for the MEK1/2 allosteric site, and generally has superior pharmacokinetics. A randomized phase II trial of docetaxel with and without selumetinib revealed that the combination resulted numerically superior overall survival, and a statistically significant improvement in progression-free survival and objective response rate. However, a concerning rate of hospital admission, grade 3 or 4 neutropenia, and febrile neutropenia was observed with the combination. Trials have investigated MEK inhibitors as single agents and in combination with erlotinib, and the data do not support the further development. The activity of MEK inhibitors appears to be similar in patients with KRAS mutant and wild-type NSCLC suggesting KRAS mutation status is not a reliable biomarker for efficacy. It is possible that mutations of genes in addition to KRAS mutations impact the activity of MEK inhibitors, or specific subsets of KRAS mutations may be resistant or susceptible to MEK inhibition. Other potential explanations are gene amplifications, alternative RNA splicing of genes resulting in activation of their protein products, and deregulation of noncoding RNAs and consequent altered protein expression.
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.