ArticleScience signaling2013
Receptor tyrosine kinases fall into distinct classes based on their inferred signaling networks.
Article in Science signaling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 5 citations in OpenAlex.
- Advances in targeted therapy of cholangiocarcinoma.Annals of medicine · 2024Review
- Current advances in photocatalytic proximity labeling.Cell chemical biology · 2024Review
- MicroRNAs as the critical regulators of epithelial mesenchymal transition in pancreatic tumor cells.Heliyon · 2024Review
- Functional signaling test identifies HER2 negative breast cancer patients who may benefit from c-Met and pan-HER combination therapy.Cell communication and signaling : CCS · 2022Article
- Intrahepatic Cholangiocarcinoma: A Summative Review of Biomarkers and Targeted Therapies.Cancers · 2021Review
- Potentiating Therapeutic Effects of Epidermal Growth Factor Receptor Inhibition in Triple-Negative Breast Cancer.Pharmaceuticals (Basel, Switzerland) · 2021Review
- When the MET receptor kicks in to resist targeted therapies.Oncogene · 2021Review
- Article
- Apoptosis of cancer cells is triggered by selective crosslinking and inhibition of receptor tyrosine kinases.Communications biology · 2019Article
- Genomic Status ofCancer research · 2018Article
- Receptor tyrosine kinases (RTKs) in breast cancer: signaling, therapeutic implications and challenges.Molecular cancer · 2018Review
- Quantification of growth factor signaling and pathway cross talk by live-cell imaging.American journal of physiology. Cell physiology · 2017Article
- High-Content Imaging Platform for Profiling Intracellular Signaling Network Activity in Living Cells.Cell chemical biology · 2016Article
- Article
- TetraMabs: simultaneous targeting of four oncogenic receptor tyrosine kinases for tumor growth inhibition in heterogeneous tumor cell populations.Protein engineering, design & selection : PEDS · 2016Article
- Reverse Phase Protein Arrays for Compound Profiling.Current protocols in chemical biology · 2016Article
- Tuning cell migration: contractility as an integrator of intracellular signals from multiple cues.F1000Research · 2016Review
- Integrating Murine and Clinical Trials with Cabozantinib to Understand Roles of MET and VEGFR2 as Targets for Growth Inhibition of Prostate Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- PEA3 transcription factors are downstream effectors of Met signaling involved in migration and invasiveness of Met-addicted tumor cells.Molecular oncology · 2015Article
- Multiscale analysis of the murine intestine for modeling human diseases.Integrative biology : quantitative biosciences from nano to macro · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Although many anticancer drugs that target receptor tyrosine kinases (RTKs) provide clinical benefit, their long-term use is limited by resistance that is often attributed to increased abundance or activation of another RTK that compensates for the inhibited receptor. To uncover common and unique features in the signaling networks of RTKs, we measured time-dependent signaling in six isogenic cell lines, each expressing a different RTK as downstream proteins were systematically perturbed by RNA interference. Network models inferred from the data revealed a conserved set of signaling pathways and RTK-specific features that grouped the RTKs into three distinct classes: (i) an EGFR/FGFR1/c-Met class constituting epidermal growth factor receptor, fibroblast growth factor receptor 1, and the hepatocyte growth factor receptor c-Met; (ii) an IGF-1R/NTRK2 class constituting insulin-like growth factor 1 receptor and neurotrophic tyrosine receptor kinase 2; and (iii) a PDGFRβ class constituting platelet-derived growth factor receptor β. Analysis of cancer cell line data showed that many RTKs of the same class were coexpressed and that increased abundance of an RTK or its cognate ligand frequently correlated with resistance to a drug targeting another RTK of the same class. In contrast, abundance of an RTK or ligand of one class generally did not affect sensitivity to a drug targeting an RTK of a different class. Thus, classifying RTKs by their inferred networks and then therapeutically targeting multiple receptors within a class may delay or prevent the onset of resistance.
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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.