ArticleCell2012
Dynamic reprogramming of the kinome in response to targeted MEK inhibition in triple-negative breast cancer.
Article in Cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 473 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
473 citing papers in PubMed, 734 citations in OpenAlex.
- Selumetinib in adults with NF1 and inoperable plexiform neurofibroma: a phase 2 trial.Nature medicine · 2025Trial
- Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children's Oncology Group.Cancer discovery · 2024Trial
- Cabozantinib for neurofibromatosis type 1-related plexiform neurofibromas: a phase 2 trial.Nature medicine · 2021Trial
- Dynamic genetic and nongenetic RAS-pathway activation drives resistance to FLT3 and BCL2 inhibitor therapy.Blood · 2026Article
- Review
- Article
- Kinase Plasticity with Vandetanib Treatment Enhances Sensitivity to Tamoxifen in Estrogen Receptor Positive Breast Cancer.Molecular cancer therapeutics · 2026Article
- Advances in the design and discovery of small-molecule tyrosine kinase inhibitors for breast cancer.RSC advances · 2026Review
- Phosphoproteomic Profiling Identifies PAK4 S474 Phosphorylation Affects Docetaxel Chemosensitivity via Modulation of Microtubule Stabilization in Breast Cancer.Biomedicines · 2026Article
- Acquisition of Resistance to RAS Inhibition Is Associated with the Upregulation of Macropinocytosis through Both PI3K-Dependent and -Independent Signaling.Cancer research communications · 2026Article
- A Constellation of Fluorescent Biosensors to Illuminate the Galaxy of Protein Kinases.Chembiochem : a European journal of chemical biology · 2026Review
- Structure-Based Design, Synthesis, and Evaluation of Novel Ponatinib Derivatives With a Significantly Altered Selectivity Profile.ChemMedChem · 2026Article
- Proteomic approaches for interrogating kinase signaling networks.The Journal of investigative dermatology · 2026Article
- Potent and selective LSD1 inhibitor DC551040 reveals a promising combination therapy for AML with insight into epigenetic dysregulation.Signal transduction and targeted therapy · 2026Article
- RIPK1 regulates β-cell fate via actions on gene expression and kinase signaling in a mouse model of β-cell self-reactivity.Cell death & disease · 2026Article
- RAS Mutation-Specific Responses to Paralog- and State-Selective RAS Inhibitors.Molecular cancer research : MCR · 2026Article
- Decyl caffeate inhibits the proliferation of human triple negative breast cancer cells.BioMedicine · 2026Article
- Proteomic Analysis of PTEN-Deficient Cells Reveals Src-Mediated Upregulation of EphA2 and Therapeutic Potential of Dual Inhibition.Molecular & cellular proteomics : MCP · 2025Article
- Intra-tumoral hypoxia promotes CD8Immunity · 2025Article
- Defining the MYC-regulated transcriptome and kinome that support KRAS- and ERK-dependent growth of pancreatic cancer.Science signaling · 2025Article
413 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
27 authors at 1 institution in 1 country.
Funding
Abstract
Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple-negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK induction by MEK inhibitors, and prevention of proteasomal c-Myc degradation blocked kinome reprogramming. MEK inhibitor-induced RTK stimulation overcame MEK2 inhibition, but not MEK1 inhibition, reactivating ERK and producing drug resistance. The C3Tag GEMM for TNBC similarly induced RTKs in response to MEK inhibition. The inhibitor-induced RTK profile suggested a kinase inhibitor combination therapy that produced GEMM tumor apoptosis and regression where single agents were ineffective. This approach defines mechanisms of drug resistance, allowing rational design of combination therapies for cancer.
Indexed as
Identifiers
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.