ArticleeLife2015
Perturbation biology nominates upstream-downstream drug combinations in RAF inhibitor resistant melanoma cells.
Article in eLife, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 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.
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Who cites it
65 citing papers in PubMed, 119 citations in OpenAlex.
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- Model-based inference of enzyme inhibitions from perturbation-induced metabolic dynamics.bioRxiv : the preprint server for biology · 2026Article
- BET inhibition disrupts the FOXM1-MYC axis to induce BRCAness and enhance PARP inhibitor response.NPJ precision oncology · 2026Article
- Reconstructing and comparing signal transduction networks from single-cell protein quantification data.Bioinformatics (Oxford, England) · 2026Article
- Cancer-on-a-chip for precision cancer medicine.Lab on a chip · 2025Review
- R2HaPpY: Rapid-robust phosphotyrosine peptide enrichment using HaloTag-Src SH2 pY superbinder.bioRxiv : the preprint server for biology · 2025Article
- Vertical inhibition of p110α/AKT and N-cadherin enhances treatment efficacy in PIK3CA-aberrated ovarian cancer cells.Molecular oncology · 2025Article
- Causal models and prediction in cell line perturbation experiments.BMC bioinformatics · 2025Article
- AI-empowered perturbation proteomics for complex biological systems.Cell genomics · 2024Article
- Unveiling hidden connections in omics data via pyPARAGON: an integrative hybrid approach for disease network construction.Briefings in bioinformatics · 2024Article
- Recent Trends in Nanocarrier-Based Drug Delivery System for Prostate Cancer.AAPS PharmSciTech · 2024Review
- Functional and spatial proteomics profiling reveals intra- and intercellular signaling crosstalk in colorectal cancer.iScience · 2023Article
- Antibody reliability influences observed mRNA-protein correlations in tumour samples.Life science alliance · 2023Article
- A comprehensive mechanistic model of adipocyte signaling with layers of confidence.NPJ systems biology and applications · 2023Article
- Mapping the functional interactions at the tumor-immune checkpoint interface.Communications biology · 2023Article
- BET inhibitors synergize with sunitinib in melanoma through GDF15 suppression.Experimental & molecular medicine · 2023Article
- Application of perturbation gene expression profiles in drug discovery-From mechanism of action to quantitative modelling.Frontiers in systems biology · 2023Review
- Hypothesis-generating proteome perturbation to identify NEU-4438 and acoziborole modes of action in the African Trypanosome.iScience · 2022Article
- BET inhibition induces vulnerability to MCL1 targeting through upregulation of fatty acid synthesis pathway in breast cancer.Cell reports · 2022Article
- Identifying mutant-specific multi-drug combinations using comparative network reconstruction.iScience · 2022Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Resistance to targeted cancer therapies is an important clinical problem. The discovery of anti-resistance drug combinations is challenging as resistance can arise by diverse escape mechanisms. To address this challenge, we improved and applied the experimental-computational perturbation biology method. Using statistical inference, we build network models from high-throughput measurements of molecular and phenotypic responses to combinatorial targeted perturbations. The models are computationally executed to predict the effects of thousands of untested perturbations. In RAF-inhibitor resistant melanoma cells, we measured 143 proteomic/phenotypic entities under 89 perturbation conditions and predicted c-Myc as an effective therapeutic co-target with BRAF or MEK. Experiments using the BET bromodomain inhibitor JQ1 affecting the level of c-Myc protein and protein kinase inhibitors targeting the ERK pathway confirmed the prediction. In conclusion, we propose an anti-cancer strategy of co-targeting a specific upstream alteration and a general downstream point of vulnerability to prevent or overcome resistance to targeted drugs.
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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.