ArticleCancer cell2012
Therapeutic effect of γ-secretase inhibition in KrasG12V-driven non-small cell lung carcinoma by derepression of DUSP1 and inhibition of ERK.
Article in Cancer cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 118 citations in OpenAlex.
- Pooled it
- NOTCH pathway inactivation promotes bladder cancer progression.The Journal of clinical investigation · 2015Trial
- NOTCH1 intracellular domain stabilization by MDM2 plays a major role in NSCLC response to platinum.EMBO molecular medicine · 2026Article
- Dual-Specificity Protein Phosphatases Targeting Extracellular Signal-Regulated Kinases: Friends or Foes in the Biology of Cancer?International journal of molecular sciences · 2025Review
- Notch Signaling in Drosophila Tumor Models.Advances in experimental medicine and biology · 2025Review
- Chronic lung inflammation and CK14+ basal cell proliferation induce persistent alveolar-bronchiolization in SARS-CoV-2-infected hamsters.EBioMedicine · 2024Article
- Article
- The role of alternative splicing in lung cancer.Cancer chemotherapy and pharmacology · 2023Review
- Notch pathway regulates osimertinib drug-tolerant persistence in EGFR-mutated non-small-cell lung cancer.Cancer science · 2023Article
- RO4929097, a Selective γ-Secretase Inhibitor, Inhibits Subretinal Fibrosis Via Suppressing Notch and ERK1/2 Signaling in Laser-Induced Mouse Model.Investigative ophthalmology & visual science · 2022Article
- A γ-Secretase Inhibitor Attenuates Cell Cycle Progression and Invasion in Human Oral Squamous Cell Carcinoma: An In Vitro Study.International journal of molecular sciences · 2022Article
- Targeting DUSP Activity as a Treatment for High-Grade Serous Ovarian Carcinoma.Molecular cancer therapeutics · 2022Article
- DUSP7 inhibits cervical cancer progression by inactivating the RAS pathway.Journal of cellular and molecular medicine · 2021Article
- Smarcd1 Inhibits the Malignant Phenotypes of Human Glioblastoma Cells via Crosstalk with Notch1.Molecular neurobiology · 2021Article
- Nanog maintains stemness of Lkb1-deficient lung adenocarcinoma and prevents gastric differentiation.EMBO molecular medicine · 2021Article
- Notch Transduction in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2020Review
- Notch inhibition overcomes resistance to tyrosine kinase inhibitors in EGFR-driven lung adenocarcinoma.The Journal of clinical investigation · 2020Article
- Precision medicine for human cancers with Notch signaling dysregulation (Review).International journal of molecular medicine · 2020Review
- Tomatidine Represses Invasion and Migration of Human Osteosarcoma U2OS and HOS Cells by Suppression of Presenilin 1 and c-Raf-MEK-ERK Pathway.Molecules (Basel, Switzerland) · 2020Article
- Peroxiredoxins and Beyond; Redox Systems Regulating Lung Physiology and Disease.Antioxidants & redox signaling · 2019Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Here, we have investigated the role of the Notch pathway in the generation and maintenance of Kras(G12V)-driven non-small cell lung carcinomas (NSCLCs). We demonstrate by genetic means that γ-secretase and RBPJ are essential for the formation of NSCLCs. Of importance, pharmacologic treatment of mice carrying autochthonous NSCLCs with a γ-secretase inhibitor (GSI) blocks cancer growth. Treated carcinomas present reduced HES1 levels and reduced phosphorylated ERK without changes in phosphorylated MEK. Mechanistically, we show that HES1 directly binds to and represses the promoter of DUSP1, encoding a dual phosphatase that is active against phospho-ERK. Accordingly, GSI treatment upregulates DUSP1 and decreases phospho-ERK. These data provide proof of the in vivo therapeutic potential of GSIs in primary NSCLCs.
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.