ArticleNature communications2024
CRISPR screens reveal convergent targeting strategies against evolutionarily distinct chemoresistance in cancer.
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Article in Nature communications, 2024. 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 33 papers.
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33citing papers in PubMed
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33 citing papers in PubMed.
- Targeting receptor tyrosine kinases: from molecular mechanisms to clinical therapeutics.Signal transduction and targeted therapy · 2026Review
- CRISPR in clinical oncology: translational advances from molecular diagnostics to therapeutics.Nature reviews. Clinical oncology · 2026Review
- Heterogeneity in cancer: molecular mechanisms and therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- CRISPR Technologies in Type 2 Diabetes: From Mechanistic Insights to Therapeutic Discovery.International journal of molecular sciences · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Global landscape of protein-coding and long non-coding RNA alternative splicing and regulation in the human esophageal squamous cell carcinoma.Cancer cell international · 2026Article
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- Comprehensive analysis of metabolic reprogramming-related gene signatures for predicting ovarian cancer prognosis, the immune landscape, and potential treatment options.Discover oncology · 2026Article
- Functional CRISPR Screens Define Genetic Drivers for Cancer Transformation and Progression from Non-Cancerous Cells.International journal of molecular sciences · 2026Article
- Article
- Serum Metabolomic Profiles Predict Sensitivity and Toxicity to Platinum- Fluorouracil Chemotherapy in a Gastric Cancer Xenograft Model.Combinatorial chemistry & high throughput screening · 2026Article
- Review
- Synergistic effect study on the co-delivery of paclitaxel and SiRNA targeting STMN1 based on MPDA nanoparticles in the therapy of ovarian cancer.Journal of nanobiotechnology · 2025Article
- Target Discovery in Head-and-Neck Squamous Cell Carcinoma: Genome-Wide CRISPR Screens Illuminate Therapeutic Resistance and Actionable Dependencies.Biomedicines · 2025Review
- Article
- Advances and Challenges in Drug Screening for Cancer Therapy: A Comprehensive Review.Bioengineering (Basel, Switzerland) · 2025Review
- Applications of Genome-wide Screening of CRISPR/Cas9 Knockout Library in Identifying Novel Molecular Targets for Xenobiotics.Environment & health (Washington, D.C.) · 2025Review
- Polo-like kinase 4 (PLK4) as a therapeutic target in breast cancer.Carcinogenesis · 2025Review
- EMT and cancer stem cells: Drivers of therapy resistance and promising therapeutic targets.Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy · 2025Review
- Single-Cell Transcriptomics: Technical Advances, Applications and Challenges in Cancer Drug Discovery.Current cancer drug targets · 2025Article
Corrections and comments
- Erratum issued
Authors and funding
35 authors.
Chunge Zhong *Key Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.ORCID 0009-0000-7017-7459
Wen-Jie Jiang *Peking University Third Hospital, Beijing, 100191, China.ORCID 0009-0009-9678-9889
Yingjia YaoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Zexu LiKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.ORCID 0000-0002-4685-4656
You LiKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Shengnan WangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Xiaofeng WangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Wenjuan ZhuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Siqi WuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Jing WangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Shuangshuang FanKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Shixin MaKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Yeshu LiuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Han ZhangKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Wenchang ZhaoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Lu ZhaoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Yi FengKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Zihan LiKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.ORCID 0000-0001-5082-9560
Ruifang GuoKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Li YuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Fengyun PeiDepartment of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Jun HuClinical Research Center, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Xingzhi FengGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Zihuan YangGuangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Diseases, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.ORCID 0000-0002-0244-3214
Zhengjia YangDepartment of Cardiothoracic Surgery, Jinqiu Hospital of Liaoning Province, Shenyang, China.
Xueying YangDepartment of Thoracic Surgery, The Fourth Affiliated Hospital of China Medical University, Shenyang, China.
Yue HouKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.ORCID 0000-0002-5040-9344
Danni ZhangKey Laboratory for Anisotropy and Texture of Materials (Ministry of Education), School of Materials Science and Engineering, Northeastern University, Shenyang, China.
Dake XuKey Laboratory for Anisotropy and Texture of Materials (Ministry of Education), School of Materials Science and Engineering, Northeastern University, Shenyang, China.ORCID 0000-0003-0931-7189
Ren ShengKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.ORCID 0000-0002-2293-8986
Yihao LiBeiGene Institute, BeiGene (Shanghai) Research & Development Co., Ltd, 200131, Shanghai, China.
Lijun LiuKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China.
Hua-Jun WuKey laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Peking University Cancer Hospital & Institute, Beijing, 100142, China. hjwu@pku.edu.cn.ORCID 0000-0003-3498-3095
Jun HuangDepartment of Colorectal Surgery, the Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. huangj97@mail.sysu.edu.cn.
Teng FeiKey Laboratory of Bioresource Research and Development of Liaoning Province, College of Life and Health Sciences, Northeastern University, Shenyang, 110819, China. feiteng@mail.neu.edu.cn.ORCID 0000-0001-9620-0450
Funding
National Natural Science Foundation of China (National Science Foundation of China) 31871344; 32071441
Abstract
Resistance to chemotherapy has been a major hurdle that limits therapeutic benefits for many types of cancer. Here we systematically identify genetic drivers underlying chemoresistance by performing 30 genome-scale CRISPR knockout screens for seven chemotherapeutic agents in multiple cancer cells. Chemoresistance genes vary between conditions primarily due to distinct genetic background and mechanism of action of drugs, manifesting heterogeneous and multiplexed routes towards chemoresistance. By focusing on oxaliplatin and irinotecan resistance in colorectal cancer, we unravel that evolutionarily distinct chemoresistance can share consensus vulnerabilities identified by 26 second-round CRISPR screens with druggable gene library. We further pinpoint PLK4 as a therapeutic target to overcome oxaliplatin resistance in various models via genetic ablation or pharmacological inhibition, highlighting a single-agent strategy to antagonize evolutionarily distinct chemoresistance. Our study not only provides resources and insights into the molecular basis of chemoresistance, but also proposes potential biomarkers and therapeutic strategies against such resistance.
Indexed as
Antineoplastic AgentsCRISPR-Cas SystemsDrug Resistance, NeoplasmIrinotecanOxaliplatinProtein Serine-Threonine KinasesAnimalsCell Line, TumorClustered Regularly Interspaced Short Palindromic RepeatsColorectal NeoplasmsGene Expression Regulation, NeoplasticHumansMiceNeoplasmsAntineoplastic AgentsIrinotecanOxaliplatinPLK4 protein, humanProtein Serine-Threonine Kinases
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