ArticleOncotarget2016
Modeling of signaling crosstalk-mediated drug resistance and its implications on drug combination.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 62 citations in OpenAlex.
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- CanSeer: a translational methodology for developing personalized cancer models and therapeutics.Scientific reports · 2025Article
- SynDRep: a synergistic partner prediction tool based on knowledge graph for drug repurposing.Bioinformatics advances · 2025Article
- Sesquiterpene lactones as emerging biomolecules to cease cancer by targeting apoptosis.Frontiers in pharmacology · 2024Review
- DFFNDDS: prediction of synergistic drug combinations with dual feature fusion networks.Journal of cheminformatics · 2023Article
- DEML: Drug Synergy and Interaction Prediction Using Ensemble-Based Multi-Task Learning.Molecules (Basel, Switzerland) · 2023Article
- A review of deep learning applications in human genomics using next-generation sequencing data.Human genomics · 2022Review
- Machine learning methods, databases and tools for drug combination prediction.Briefings in bioinformatics · 2022Article
- XDeathDB: a visualization platform for cell death molecular interactions.Cell death & disease · 2021Article
- Prediction of synergistic drug combinations using PCA-initialized deep learning.BioData mining · 2021Article
- Co-Targeting Plk1 and DNMT3a in Advanced Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
- GLI1 reduces drug sensitivity by regulating cell cycle through PI3K/AKT/GSK3/CDK pathway in acute myeloid leukemia.Cell death & disease · 2021Article
- Anticancer drug synergy prediction in understudied tissues using transfer learning.Journal of the American Medical Informatics Association : JAMIA · 2021Article
- The Crosstalk between FAK and Wnt Signaling Pathways in Cancer and Its Therapeutic Implication.International journal of molecular sciences · 2020Review
- Parallel Tempering with Lasso for model reduction in systems biology.PLoS computational biology · 2020Article
- A Proteomic Connectivity Map for Characterizing the Tumor Adaptive Response to Small Molecule Chemical Perturbagens.ACS chemical biology · 2020Article
- Pathway-Based Drug-Repurposing Schemes in Cancer: The Role of Translational Bioinformatics.Frontiers in oncology · 2020Review
- PTPRS drives adaptive resistance to MEK/ERK inhibitors through SRC.Oncotarget · 2019Article
- Differential regulatory network-based quantification and prioritization of key genes underlying cancer drug resistance based on time-course RNA-seq data.PLoS computational biology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of pharmacological perturbation to the signaling transduction network depends on the network topology. However, whether and how signaling dynamics mediated by crosstalk contributes to the drug resistance are not fully understood and remain to be systematically explored. In this study, motivated by a realistic signaling network linked by crosstalk between EGF/EGFR/Ras/MEK/ERK pathway and HGF/HGFR/PI3K/AKT pathway, we develop kinetic models for several small networks with typical crosstalk modules to investigate the role of the architecture of crosstalk in inducing drug resistance. Our results demonstrate that crosstalk inhibition diminishes the response of signaling output to the external stimuli. Moreover, we show that signaling crosstalk affects the relative sensitivity of drugs, and some types of crosstalk modules that could yield resistance to the targeted drugs were identified. Furthermore, we quantitatively evaluate the relative efficacy and synergism of drug combinations. For the modules that are resistant to the targeted drug, we identify drug targets that can not only increase the relative drug efficacy but also act synergistically. In addition, we analyze the role of the strength of crosstalk in switching a module between drug-sensitive and drug-resistant. Our study provides mechanistic insights into the signaling crosstalk-mediated mechanisms of drug resistance and provides implications for the design of synergistic drug combinations to reduce drug 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.