ReviewCell death discovery2021
Genome-scale CRISPR-Cas9 knockout screening in hepatocellular carcinoma with lenvatinib resistance.
Review in Cell death discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 46 papers.
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
46 citing papers in PubMed, 79 citations in OpenAlex.
- NEK7-induced phosphorylation of EGFR on serine 1070 drives the acquired lenvatinib resistance in hepatocellular carcinoma.Hepatology (Baltimore, Md.) · 2026Article
- CRISPR Screening in Hepatocellular Carcinoma: From Tumor Progression to Immune Evasion and Therapeutic Resistance.International journal of molecular sciences · 2026Review
- CRISPR-Cas9 Screening and Simulated Infection Transcriptomic Identify Key Drivers of Innate Immunity in Bactrian Camels.Animals : an open access journal from MDPI · 2026Article
- Repositioning Antihistamine for Cancer Therapy: Clemizole as a Template for the Design of Liver Tissue-Targeting Epigenetic-Modifying Agents.Journal of medicinal chemistry · 2026Article
- Analyses of the Coexpression of Lactate Metabolism- and Ferroptosis-Related Genes in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2026Article
- Loss of ELF2 drives topotecan resistance in retinoblastoma revealed by genome-wide CRISPR-Cas9 screening.Cell death & disease · 2025Article
- Targeting Kinase Suppressor of Ras 1 (KSR1) for Cancer Therapy.Pharmaceutics · 2025Review
- Neurofibromin Encoded by theInternational journal of molecular sciences · 2025Article
- Local therapy overcomes primary resistance to target-immunotherapy combination in unresectable hepatocellular carcinoma.Cancer immunology, immunotherapy : CII · 2025Article
- Hepatocellular carcinoma drug resistance models.Cancer cell international · 2025Review
- CircRNA-mTOR Promotes Hepatocellular Carcinoma Progression and Lenvatinib Resistance Through the PSIP1/c-Myc Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- CRISPR/Cas9 system: a novel approach to overcome chemotherapy and radiotherapy resistance in cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Review
- PathSynergy: a deep learning model for predicting drug synergy in liver cancer.Briefings in bioinformatics · 2025Article
- Review
- High mobility group protein N2 inhibits the progression of hepatocellular carcinoma and the related molecular mechanisms.Cytotechnology · 2025Article
- Review
- Article
- Genomic Amplification of TBC1D31 Promotes Hepatocellular Carcinoma Through Reducing the Rab22A-Mediated Endolysosomal Trafficking and Degradation of EGFR.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- The p-MYH9/USP22/HIF-1α axis promotes lenvatinib resistance and cancer stemness in hepatocellular carcinoma.Signal transduction and targeted therapy · 2024Article
- Silencing MFN2 Drives WNT/β-catenin Nucleation to Reduce Sorafenib Sensitivity in Hepatocellular Carcinoma Cells.Current medical science · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Lenvatinib is the first target drug approved for advanced hepatocellular carcinoma (HCC). However, the development of drug resistance is common, and the mechanisms of lenvatinib resistance and resistant targets in HCC are poorly understood. By using CRISPR/Cas9 library screening, we screened out two key resistance genes, neurofibromin 1(NF1), and dual specificity phosphatase 9 (DUSP9), as critical drivers for lenvatinib resistance in HCC. With RNAi knockdown and CRISPR/Cas9 knockout models, we further clarified the mechanisms by which NF1 loss reactivates the PI3K/AKT and MAPK/ERK signaling pathways, while DUSP9 loss activates the MAPK/ERK signaling pathways, thereby inactivating FOXO3, followed by degradation of FOXO3, finally induced lenvatinib resistance. We also screened out trametinib, a small molecule pathway inhibitor for MEK, that can be used to reverse resistance induced by NF1 and DUSP9 loss in HCC cells. Trametinib was still able to halt HCC growth even when NF1 was knocked out in mice. Collectively, the findings indicate that NF1 and DUSP9 takes critical role in lenvatinib resistance and may be novel specific targets and predictive markers for lenvatinib resistance in HCC.
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.