ArticleNature communications2023
A CRISPR-drug perturbational map for identifying compounds to combine with commonly used chemotherapeutics.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Dysregulated AKT signaling reprograms osteosarcoma to drive selective reliance on EP300.The Journal of experimental medicine · 2026Article
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- DNA-PKcs promotes therapy resistance and metastatic recurrence in neuroblastoma.Cancer letters · 2026Article
- CDK2 inhibition promotes neuronal differentiation in neuroblastoma.Scientific reports · 2026Article
- NPCDR 2.0: the activity and structure landscape of natural product-based drug combination.Nucleic acids research · 2026Article
- Defining treatment-resistant brain cancer: Genetic screening to identify oncogene-driven immunomodulation and therapy resistance.Cancer gene therapy · 2026Review
- An open-source screening platform accelerates discovery of drug combinations.Nature communications · 2025Article
- Advances and Challenges in Drug Screening for Cancer Therapy: A Comprehensive Review.Bioengineering (Basel, Switzerland) · 2025Review
- Single-Cell Transcriptomics: Technical Advances, Applications and Challenges in Cancer Drug Discovery.Current cancer drug targets · 2025Article
- Transcriptomic and Functional Validation Reveals PAQR3/P6-55 as Potential Therapeutic Targets in Colon Cancer.Biology · 2025Article
- Interplay Between the Epigenome, the Microenvironment, and the Immune System in Neuroblastoma.Cancers · 2025Review
- Bone morphogenetic protein (BMP) signaling determines neuroblastoma cell fate and sensitivity to retinoic acid.Nature communications · 2025Article
- The present and future of the Cancer Dependency Map.Nature reviews. Cancer · 2025Review
- Article
- Paralogue-selective degradation of the lysine acetyltransferase EP300.bioRxiv : the preprint server for biology · 2024Article
- Review
Corrections and comments
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Authors and funding
21 authors at 2 institutions in 1 country.
Funding
Abstract
Combination chemotherapy is crucial for successfully treating cancer. However, the enormous number of possible drug combinations means discovering safe and effective combinations remains a significant challenge. To improve this process, we conduct large-scale targeted CRISPR knockout screens in drug-treated cells, creating a genetic map of druggable genes that sensitize cells to commonly used chemotherapeutics. We prioritize neuroblastoma, the most common extracranial pediatric solid tumor, where ~50% of high-risk patients do not survive. Our screen examines all druggable gene knockouts in 18 cell lines (10 neuroblastoma, 8 others) treated with 8 widely used drugs, resulting in 94,320 unique combination-cell line perturbations, which is comparable to the largest existing drug combination screens. Using dense drug-drug rescreening, we find that the top CRISPR-nominated drug combinations are more synergistic than standard-of-care combinations, suggesting existing combinations could be improved. As proof of principle, we discover that inhibition of PRKDC, a component of the non-homologous end-joining pathway, sensitizes high-risk neuroblastoma cells to the standard-of-care drug doxorubicin in vitro and in vivo using patient-derived xenograft (PDX) models. Our findings provide a valuable resource and demonstrate the feasibility of using targeted CRISPR knockout to discover combinations with common chemotherapeutics, a methodology with application across all cancers.
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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.