ArticleOncogenesis2019
A functional CRISPR/Cas9 screen identifies kinases that modulate FGFR inhibitor response in gastric cancer.
Article in Oncogenesis, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Review
- Unraveling the FGFR-RNA splicing axis: Mechanisms, oncogenic crosstalks and innovations for therapeutic purpose.Acta pharmaceutica Sinica. B · 2026Review
- Characterizing common loss-of-function genes and their potential utility in assessing population variability and chemical susceptibility.bioRxiv : the preprint server for biology · 2025Article
- Precision Antibody Therapy in Gastric and Gastroesophageal Cancer: Targeting FGFR2b, CLDN18.2, and VEGFR2.Cells · 2025Review
- The Role of FGFR2 as a Novel Biomarker for Treatment of Gastric Cancer-A Literature Review.Medicina (Kaunas, Lithuania) · 2025Review
- RESTRICT-seq enables time-gated CRISPR screens and uncovers novel epigenetic dependencies of SCC resistance.bioRxiv : the preprint server for biology · 2025Article
- Perturbomics: CRISPR-Cas screening-based functional genomics approach for drug target discovery.Experimental & molecular medicine · 2025Review
- Reverse-Phase Protein Microarrays for OverexpressedAnalytical chemistry · 2024Article
- Review
- TTD: Therapeutic Target Database describing target druggability information.Nucleic acids research · 2024Article
- CRISPR/Cas9 systems: Delivery technologies and biomedical applications.Asian journal of pharmaceutical sciences · 2023Review
- Ten Years of CRISPRing Cancers In Vitro.Cancers · 2022Review
- CRISPR/Cas9 Genome-Editing Technology and Potential Clinical Application in Gastric Cancer.Genes · 2022Review
- EPIKOL, a chromatin-focused CRISPR/Cas9-based screening platform, to identify cancer-specific epigenetic vulnerabilities.Cell death & disease · 2022Article
- New approaches to moderate CRISPR-Cas9 activity: Addressing issues of cellular uptake and endosomal escape.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Evolution of Molecular Targeted Cancer Therapy: Mechanisms of Drug Resistance and Novel Opportunities Identified by CRISPR-Cas9 Screening.Frontiers in oncology · 2022Review
- Fibroblast growth factor receptors in cancer: genetic alterations, diagnostics, therapeutic targets and mechanisms of resistance.British journal of cancer · 2021Review
- CRISPR/Cas9 in Gastrointestinal Malignancies.Frontiers in cell and developmental biology · 2021Review
- Genome-scale CRISPRa screening identifies MTX1 as a contributor for sorafenib resistance in hepatocellular carcinoma by augmenting autophagy.International journal of biological sciences · 2021Article
- A Genome-Scale CRISPR Knock-Out Screen Identifies MicroRNA-5197-5p as a Promising Radiosensitive Biomarker in Colorectal Cancer.Frontiers in oncology · 2021Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Some gastric cancers have FGFR2 amplifications, making them sensitive to FGFR inhibitors. However, cancer cells inevitably develop resistance despite initial response. The underlying resistance mechanism to FGFR inhibition is unclear. In this study, we applied a kinome-wide CRISPR/Cas9 screen to systematically identify kinases that are determinants of sensitivity to a potent FGFR inhibitor AZD4547 in KatoIII cells, a gastric cancer cell line with FGFR2 amplification. In total, we identified 20 kinases, involved in ILK, SRC, and EGFR signaling pathways, as determinants that alter cell sensitivity to FGFR inhibition. We functionally validated the top negatively selected and positively selected kinases, ILK and CSK, from the CRISPR/Cas9 screen using RNA interference. We observed synergistic effects on KatoIII cells as well as three additional gastric cancer cell lines with FGFR2 amplification when AZD4547 was combined with small molecular inhibitors Cpd22 and lapatinib targeting ILK and EGFR/HER2, respectively. Furthermore, we demonstrated that GSK3b is one of the downstream effectors of ILK upon FGFR inhibition. In summary, our study systematically evaluated the kinases and associated signaling pathways modulating cell response to FGFR inhibition, and for the first time, demonstrated that targeting ILK would enhance the effectiveness of AZD4547 treatment of gastric tumors with amplifications of FGFR2.
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.