ArticleMolecular oncology2021
Genome-scale CRISPR screening identifies cell cycle and protein ubiquitination processes as druggable targets for erlotinib-resistant lung cancer.
Article in Molecular oncology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 24 citations in OpenAlex.
- Preclinical Anticipation of On- and Off-Target Resistance Mechanisms to Anti-Cancer Drugs: A Systematic Review.International journal of molecular sciences · 2024Pooled it
- Genome-wide profiling identifies the genetic dependencies of cell death following EGFR inhibition.The Journal of biological chemistry · 2026Article
- GRIP-Lung: Generative Model of Response to Drug-Induced Perturbation in Lung Cancer.International journal of molecular sciences · 2026Article
- Statistical inference with a manifold-constrained RNA velocity model uncovers cell cycle speed modulations.Nature methods · 2024Article
- Targeting Hdm2 and Hdm4 in Anticancer Drug Discovery: Implications for Checkpoint Inhibitor Immunotherapy.Cells · 2024Review
- CRISPR/Cas9 gene editing: a novel strategy for fighting drug resistance in respiratory disorders.Cell communication and signaling : CCS · 2024Review
- MIG6 loss confers resistance to ALK/ROS1 inhibitors in NSCLC through EGFR activation by low-dose EGF.JCI insight · 2023Article
- Novel Molecular Subtyping Scheme Based on In Silico Analysis of Cuproptosis Regulator Gene Patterns Optimizes Survival Prediction and Treatment of Hepatocellular Carcinoma.Journal of clinical medicine · 2023Article
- The APC/C E3 ligase subunit ANAPC11 mediates FOXO3 protein degradation to promote cell proliferation and lymph node metastasis in urothelial bladder cancer.Cell death & disease · 2023Article
- Applying CRISPR-Cas9 screens to dissect hematological malignancies.Blood advances · 2023Review
- High throughput sequencing revealed enhanced cell cycle signaling in SLE patients.Scientific reports · 2023Article
- The roles of protein ubiquitination in tumorigenesis and targeted drug discovery in lung cancer.Frontiers in endocrinology · 2023Review
- Genome-wide CRISPR/Cas9 screening for drug resistance in tumors.Frontiers in pharmacology · 2023Review
- Current methodologies in protein ubiquitination characterization: from ubiquitinated protein to ubiquitin chain architecture.Cell & bioscience · 2022Review
- Genome-Wide CRISPR Screening Identifies DCK and CCNL1 as Genes That Contribute to Gemcitabine Resistance in Pancreatic Cancer.Cancers · 2022Article
- Application and Prospect of CRISPR/Cas9 Technology in Reversing Drug Resistance of Non-Small Cell Lung Cancer.Frontiers in pharmacology · 2022Review
- Targeting the Proteasome in Advanced Renal Cell Carcinoma: Complexity and Limitations of Patient-Individualized Preclinical Drug Discovery.Biomedicines · 2021Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Erlotinib is highly effective in lung cancer patients with epidermal growth factor receptor (EGFR) mutations. However, despite initial favorable responses, most patients rapidly develop resistance to erlotinib soon after the initial treatment. This study aims to identify new genes and pathways associated with erlotinib resistance mechanisms in order to develop novel therapeutic strategies. Here, we induced knockout (KO) mutations in erlotinib-resistant human lung cancer cells (NCI-H820) using a genome-scale CRISPR-Cas9 sgRNA library to screen for genes involved in erlotinib susceptibility. The spectrum of sgRNAs incorporated among erlotinib-treated cells was substantially different to that of the untreated cells. Gene set analyses showed a significant depletion of 'cell cycle process' and 'protein ubiquitination pathway' genes among erlotinib-treated cells. Chemical inhibitors targeting genes in these two pathways, such as nutlin-3 and carfilzomib, increased cancer cell death when combined with erlotinib in both in vitro cell line and in vivo patient-derived xenograft experiments. Therefore, we propose that targeting cell cycle processes or protein ubiquitination pathways are promising treatment strategies for overcoming resistance to EGFR inhibitors in lung cancer.
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