ArticleNature communications2016
MEK inhibitors block growth of lung tumours with mutations in ataxia-telangiectasia mutated.
Article in Nature communications, 2016. 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
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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, 44 citations in OpenAlex.
- Targeting the DNA damage response in cancer.MedComm · 2024Review
- Synergistic combination of RAD51-SCR7 improves CRISPR-Cas9 genome editing efficiency by preventing R-loop accumulation.Molecular therapy. Nucleic acids · 2024Article
- A clinically compatible in vitro drug-screening platform identifies therapeutic vulnerabilities in primary cultures of brain metastases.Journal of neuro-oncology · 2024Article
- Complex synthetic lethality in cancer.Nature genetics · 2023Review
- ATM inhibition drives metabolic adaptation via induction of macropinocytosis.The Journal of cell biology · 2023Article
- Targeting K-Ras-mediated DNA damage response in radiation oncology: Current status, challenges and future perspectives.Clinical and translational radiation oncology · 2023Review
- Critical DNA damaging pathways in tumorigenesis.Seminars in cancer biology · 2022Review
- Cancer Cells Haploinsufficient for ATM Are Sensitized to PARP Inhibitors byInternational journal of molecular sciences · 2022Article
- Characterization of KRAS Mutation Subtypes in Non-small Cell Lung Cancer.Molecular cancer therapeutics · 2021Article
- The AML microenvironment catalyzes a stepwise evolution to gilteritinib resistance.Cancer cell · 2021Article
- Mitogen-activated protein kinase inhibition-induced modulation of epidermal growth factor receptor signaling in human head and neck squamous cell carcinoma.Head & neck · 2021Article
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- Synthetic Lethality through the Lens of Medicinal Chemistry.Journal of medicinal chemistry · 2020Review
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- Lamin B1 Overexpresses in Lung Adenocarcinoma and Promotes Proliferation in Lung Cancer Cells via AKT Pathway.OncoTargets and therapy · 2020Article
- Co-occurring genomic alterations in non-small-cell lung cancer biology and therapy.Nature reviews. Cancer · 2019Review
- miR-7 Suppresses Tumor Progression by Directly Targeting MAP3K9 in Pancreatic Cancer.Molecular therapy. Nucleic acids · 2018Article
- [Research Progress of Targeted Therapy for BRAF Mutation in Advanced Non-small Cell Lung Cancer].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 6 institutions in 4 countries.
Funding
Abstract
Lung cancer is the leading cause of cancer deaths, and effective treatments are urgently needed. Loss-of-function mutations in the DNA damage response kinase ATM are common in lung adenocarcinoma but directly targeting these with drugs remains challenging. Here we report that ATM loss-of-function is synthetic lethal with drugs inhibiting the central growth factor kinases MEK1/2, including the FDA-approved drug trametinib. Lung cancer cells resistant to MEK inhibition become highly sensitive upon loss of ATM both in vitro and in vivo. Mechanistically, ATM mediates crosstalk between the prosurvival MEK/ERK and AKT/mTOR pathways. ATM loss also enhances the sensitivity of KRAS- or BRAF-mutant lung cancer cells to MEK inhibition. Thus, ATM mutational status in lung cancer is a mechanistic biomarker for MEK inhibitor response, which may improve patient stratification and extend the applicability of these drugs beyond RAS and BRAF mutant tumours.
Indexed as
Identifiers
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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.