ArticleNature2012
Chemical genetic discovery of targets and anti-targets for cancer polypharmacology.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02363647 (Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid or Metastatic Colon Cancer), which is not on this map. Cited by 175 papers.
What it found
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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.
Personalized Cancer Therapy for Patients With Metastatic Medullary Thyroid or Metastatic Colon Cancer
Who cites it
175 citing papers in PubMed, 347 citations in OpenAlex.
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- An Unbiased Drug Screen in a Drosophila Model ofInternational journal of molecular sciences · 2026Article
- Genotype-Informed Whole-Animal Kinome Screening Reveals Shared Kinase Vulnerabilities Across Driver Contexts in PDAC.Cancer science · 2026Article
- Targeting CDKs in the RNAPII transcription cycle.Nature reviews. Drug discovery · 2026Review
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- Polypharmacology is an enduring and nearly universal property of kinase inhibitors.bioRxiv : the preprint server for biology · 2026Article
- Chemical programming of kinase inhibitors in a modular chemputer-based system.Communications biology · 2026Article
- Large Library Docking for Polypharmacology.Journal of medicinal chemistry · 2026Article
- Applications and challenges of Drosophila melanogaster as a laboratory model in human cancer research: a narrative review.Discover oncology · 2025Review
- Exploring the versatility ofFly · 2025Review
- Hemocytes facilitate interclonal cooperation-induced tumor malignancy by hijacking the innate immune system in Drosophila.The EMBO journal · 2025Article
- A stress-responsive p38 signaling axis in choanoflagellates.RSC chemical biology · 2025Article
- Structure-activity relationship studies and pharmacological evaluation of 4-phenylthiazoles as dual soluble epoxide hydrolase/fatty acid amide hydrolase inhibitors.Bioorganic & medicinal chemistry · 2025Article
- Modelling Cancer in Drosophila: Exploration to Personalised Medicine.Advances in experimental medicine and biology · 2025Review
- SVC112: From Hummingbirds to Head and Neck Cancer.Advances in experimental medicine and biology · 2025Article
- A High-Throughput Method for QuantifyingToxics · 2024Article
- Coordinated Targeting of S6K1/2 and AXL Disrupts Pyrimidine Biosynthesis in PTEN-Deficient Glioblastoma.Cancer research communications · 2024Article
- Functional exploration of copy number alterations in a Drosophila model of triple-negative breast cancer.Disease models & mechanisms · 2024Article
- Updated Toolbox for Assessing Neuronal Network Reconstruction after Cell Therapy.Bioengineering (Basel, Switzerland) · 2024Review
- All-photonic kinase inhibitors: light-controlled release-and-report inhibition.Chemical science · 2024Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The complexity of cancer has led to recent interest in polypharmacological approaches for developing kinase-inhibitor drugs; however, optimal kinase-inhibition profiles remain difficult to predict. Using a Ret-kinase-driven Drosophila model of multiple endocrine neoplasia type 2 and kinome-wide drug profiling, here we identify that AD57 rescues oncogenic Ret-induced lethality, whereas related Ret inhibitors imparted reduced efficacy and enhanced toxicity. Drosophila genetics and compound profiling defined three pathways accounting for the mechanistic basis of efficacy and dose-limiting toxicity. Inhibition of Ret plus Raf, Src and S6K was required for optimal animal survival, whereas inhibition of the 'anti-target' Tor led to toxicity owing to release of negative feedback. Rational synthetic tailoring to eliminate Tor binding afforded AD80 and AD81, compounds featuring balanced pathway inhibition, improved efficacy and low toxicity in Drosophila and mammalian multiple endocrine neoplasia type 2 models. Combining kinase-focused chemistry, kinome-wide profiling and Drosophila genetics provides a powerful systems pharmacology approach towards developing compounds with a maximal therapeutic index.
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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.