Trial reportCancer discovery2017
Enhancer Remodeling during Adaptive Bypass to MEK Inhibition Is Attenuated by Pharmacologic Targeting of the P-TEFb Complex.
Trial report in Cancer discovery, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 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
122 citing papers in PubMed, 182 citations in OpenAlex.
- Phase II study of MEK inhibitor trametinib alone and in combination with AKT inhibitor GSK2141795/uprosertib in patients with metastatic triple negative breast cancer.Breast cancer research and treatment · 2025Trial
- Aberrant JAK-STAT signaling-mediated chromatin remodeling impairs the sensitivity of NK/T-cell lymphoma to chidamide.Clinical epigenetics · 2023Trial
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- Current therapeutic interventions to target cancer stem cells for metastasis.International journal of clinical oncology · 2026Review
- Kinase Plasticity with Vandetanib Treatment Enhances Sensitivity to Tamoxifen in Estrogen Receptor Positive Breast Cancer.Molecular cancer therapeutics · 2026Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.Science advances · 2026Article
- Advances in Mechanism of Action and Efficacy of CBP/p300 Inhibitors in Different Subtypes of Breast Cancer.Molecules (Basel, Switzerland) · 2026Review
- Mevalonate pathway rewiring driven by enhancer remodelling confers resistance to KRAS inhibitors in colorectal cancer.Nature communications · 2026Article
- Resistance to the KRASG12D Inhibitor MRTX1133 Is Associated with Increased Sensitivity to BET Inhibition.Molecular cancer therapeutics · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- TTPAL inhibits the progression of breast cancer and reprograms tumor-associated macrophages by inhibiting JAK2/STAT3 signaling pathway.Breast cancer research : BCR · 2026Article
- Review
- Bromodomain-Driven Regulation of Stem Cells: A Potential Target for Cancer Therapeutic Intervention.Stem cell reviews and reports · 2026Review
- Phosphoproteome landscape of ARID1A and its implications in DNA damage response and breast cancer pathogenesis.Discover oncology · 2026Article
- Disrupting CDK9 activity suppresses triple-negative breast cancer and is enhanced by EGFR Inhibition.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Drug-tolerant persister cells in lymphoid malignancies: from mechanisms to therapeutic opportunities.Frontiers in oncology · 2026Review
- Covariate-adjusted AP-1 motif architecture and footprinting track olaparib-adaptive chromatin remodelling.Frontiers in systems biology · 2026Article
- BET proteins mediate survival mechanisms in human schwannoma model cells challenged with trametinib but not brigatinib.Oncogene · 2025Article
- Coinhibition of the MEK/RTK pathway has high therapeutic efficacy in KRAS-mutant non-small cell lung cancer.Signal transduction and targeted therapy · 2025Article
- The MEK inhibitor trametinib incurs mitochondrial injury and induces innate immune responses in the mouse heart.bioRxiv : the preprint server for biology · 2025Article
62 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
25 authors at 1 institution in 1 country.
Funding
Abstract
Targeting the dysregulated BRAF-MEK-ERK pathway in cancer has increasingly emerged in clinical trial design. Despite clinical responses in specific cancers using inhibitors targeting BRAF and MEK, resistance develops often involving nongenomic adaptive bypass mechanisms. Inhibition of MEK1/2 by trametinib in patients with triple-negative breast cancer (TNBC) induced dramatic transcriptional responses, including upregulation of receptor tyrosine kinases (RTK) comparing tumor samples before and after one week of treatment. In preclinical models, MEK inhibition induced genome-wide enhancer formation involving the seeding of BRD4, MED1, H3K27 acetylation, and p300 that drives transcriptional adaptation. Inhibition of the P-TEFb-associated proteins BRD4 and CBP/p300 arrested enhancer seeding and RTK upregulation. BRD4 bromodomain inhibitors overcame trametinib resistance, producing sustained growth inhibition in cells, xenografts, and syngeneic mouse TNBC models. Pharmacologic targeting of P-TEFb members in conjunction with MEK inhibition by trametinib is an effective strategy to durably inhibit epigenomic remodeling required for adaptive resistance.
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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.