ReviewClinical cancer research : an official journal of the American Association for Cancer Research2018
Rethinking Gamma-secretase Inhibitors for Treatment of Non-small-Cell Lung Cancer: Is Notch the Target?
Review in Clinical cancer research : an official journal of the American Association for Cancer Research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Pooled it
- CDH1 reduces endothelial cell permeability by enhancing CDH5 membrane expression under chronic intermittent hypoxia.European journal of medical research · 2025Article
- Proteolysis of TAM receptors in autoimmune diseases and cancer: what does it say to us?Cell death & disease · 2025Review
- Canonical and noncanonical NOTCH signaling in the nongenetic resistance of cancer: distinct and concerted control.Frontiers of medicine · 2025Review
- Bioinformatics Analysis and Experimental Validation of Lactylation Related Genes in Lung Adenocarcinoma.Cancer management and research · 2025Article
- Notch signaling in cancers: mechanism and potential therapy.Frontiers in cell and developmental biology · 2025Review
- SRCAP is involved in porcine reproductive and respiratory syndrome virus activated Notch signaling pathway.Journal of virology · 2024Article
- Integrated multi-omic analysis and experiment reveals the role of endoplasmic reticulum stress in lung adenocarcinoma.BMC medical genomics · 2024Article
- Inhibitors Targeting the F-BOX Proteins.Cell biochemistry and biophysics · 2023Review
- Modulation of Notch Signaling by Small-Molecular Compounds and Its Potential in Anticancer Studies.Cancers · 2023Review
- Evaluation of the anticancer activity of RIN-1, a Notch signaling modulator, in head and neck squamous cell carcinoma.Scientific reports · 2023Article
- The critical role of γ-secretase and its inhibitors in cancer and cancer therapeutics.International journal of biological sciences · 2023Review
- Low-Dose Metformin Treatment Reduces In Vitro Growth of the LL/2 Non-small Cell Lung Cancer Cell Line.Biomedicines · 2022Article
- The role of Hedgehog and Notch signaling pathway in cancer.Molecular biomedicine · 2022Review
- Loss of endothelial EMCN drives tumor lung metastasis through the premetastatic niche.Journal of translational medicine · 2022Article
- Notch signaling pathway: architecture, disease, and therapeutics.Signal transduction and targeted therapy · 2022Review
- RASSF1A disrupts the NOTCH signaling axis via SNURF/RNF4-mediated ubiquitination of HES1.EMBO reports · 2022Article
- An RFC4/Notch1 signaling feedback loop promotes NSCLC metastasis and stemness.Nature communications · 2021Article
- Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells.Scientific reports · 2021Article
- Unlocking the Secrets of Cancer Stem Cells with γ-Secretase Inhibitors: A Novel Anticancer Strategy.Molecules (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
1 author at 1 institution in 1 country.
Funding
Abstract
Lung cancer is the leading cause of cancer-related deaths among men and women. γ-Secretase inhibitors, a class of small-molecule compounds that target the Notch pathway, have been tested to treat non-small-cell lung cancer (NSCLC) in preclinical and clinical trials. Although γ-secretase inhibitors elicit a response in some tumors as single agents and sensitize NSCLC to cytotoxic and targeted therapies, they have not yet been approved for NSCLC therapy. We discuss our recently published preclinical study using the γ-secretase inhibitor AL101, formerly BMS906024, on cell lines and PDX models of NSCLC, primarily lung adenocarcinoma. We propose that Notch pathway mutations may not be the most suitable biomarker for predicting NSCLC response to γ-secretase inhibitors. γ-Secretases have over 100 known γ-secretase cleavage substrates. Many of the γ-secretase substrates are directly involved in carcinogenesis or tumor progression, and are ideal candidates to be the "on-target" biomarkers for γ-secretase inhibitors. We propose the need to systematically test the γ-secretase and other targets as potential biomarkers for sensitivity before continuing clinical trials. Now that we have entered the postgenome/transcriptome era, this goal is easily attainable. Discovery of the biomarker(s) that predict sensitivity to γ-secretase inhibitors would guide selection of the responder population that is most likely to benefit and move the compounds closer to approval for therapeutic use in NSCLC.
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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.