ArticleCancer discovery2024
Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.
Article in Cancer discovery, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 31 citations in OpenAlex.
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- Pediatric sarcomas: challenges and opportunities.Genes & development · 2026Review
- Capivasertib Combines with Trastuzumab Deruxtecan to Enhance Antitumor Activity in HER2-Positive and HER2-Low Tumors.Molecular cancer therapeutics · 2026Article
- Rethinking the role of synergy calculations in the next century of drug combination discovery.Med (New York, N.Y.) · 2026Review
- Systematic interrogation of drug sensitivities in melanoma reveals potent synergistic and antagonistic drug combinations with translational potential.Communications medicine · 2026Article
- Why in vivo models of disease remain indispensable.Disease models & mechanisms · 2026Article
- Chemical programming of kinase inhibitors in a modular chemputer-based system.Communications biology · 2026Article
- NPCDR 2.0: the activity and structure landscape of natural product-based drug combination.Nucleic acids research · 2026Article
- Synthetic lethality in cancer drug discovery: challenges and opportunities.Nature reviews. Drug discovery · 2026Review
- Cellular heterogeneity and therapeutic response profiling of human IDH + glioma stem cell cultures.Scientific reports · 2025Article
- SPARC: A Multipayload ADC Architecture for Programmable Drug Combinations.Bioconjugate chemistry · 2025Article
- Design and Optimization of Spiro-Isatin-Thiazolidinone Hybrids with Promising Anticancer Activity.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Combined MEK and PARP inhibition enhances radiation response in rectal cancer.Cell reports. Medicine · 2025Article
- A highly annotated drug combination resource for catalyzing precision combinatorial therapy.Scientific data · 2025Article
- HIG-Syn: a hypergraph and interaction-aware multigranularity network for predicting synergistic drug combinations.Bioinformatics (Oxford, England) · 2025Article
- Aurora kinases signaling in cancer: from molecular perception to targeted therapies.Molecular cancer · 2025Review
- Article
- Establishment and characterization of two novel patient-derived cell lines from myxofibrosarcoma: NCC-MFS7-C1 and NCC-MFS8-C1.Human cell · 2024Article
- GCN2 is a determinant of the response to WEE1 kinase inhibition in small-cell lung cancer.Cell reports · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
37 authors at 3 institutions in 4 countries.
Funding
Abstract
Oncology drug combinations can improve therapeutic responses and increase treatment options for patients. The number of possible combinations is vast and responses can be context-specific. Systematic screens can identify clinically relevant, actionable combinations in defined patient subtypes. We present data for 109 anticancer drug combinations from AstraZeneca's oncology small molecule portfolio screened in 755 pan-cancer cell lines. Combinations were screened in a 7 × 7 concentration matrix, with more than 4 million measurements of sensitivity, producing an exceptionally data-rich resource. We implement a new approach using combination Emax (viability effect) and highest single agent (HSA) to assess combination benefit. We designed a clinical translatability workflow to identify combinations with clearly defined patient populations, rationale for tolerability based on tumor type and combination-specific "emergent" biomarkers, and exposures relevant to clinical doses. We describe three actionable combinations in defined cancer types, confirmed in vitro and in vivo, with a focus on hematologic cancers and apoptotic targets. SIGNIFICANCE: We present the largest cancer drug combination screen published to date with 7 × 7 concentration response matrices for 109 combinations in more than 750 cell lines, complemented by multi-omics predictors of response and identification of "emergent" combination biomarkers. We prioritize hits to optimize clinical translatability, and experimentally validate novel combination hypotheses. This article is featured in Selected Articles from This Issue, p. 695.
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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.