ArticleClinical cancer research : an official journal of the American Association for Cancer Research2016
MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Antiestrogen Resistance in ER-Positive High-Grade Serous Ovarian Cancer.
Article in Clinical cancer research : an official journal of the American Association for Cancer Research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 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
39 citing papers in PubMed, 59 citations in OpenAlex.
- Trametinib versus standard of care in patients with recurrent low-grade serous ovarian cancer (GOG 281/LOGS): an international, randomised, open-label, multicentre, phase 2/3 trial.Lancet (London, England) · 2022Trial
- PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane.Journal of cancer research and clinical oncology · 2020Trial
- On the predictability of progression-free survival in ovarian cancer from NanoString gene expression data.bioRxiv : the preprint server for biology · 2026Article
- Molecular pathways in reproductive cancers: a focus on prostate and ovarian cancer.Cancer cell international · 2025Review
- Mechanisms of the JNK/p38 MAPK signaling pathway in drug resistance in ovarian cancer.Frontiers in oncology · 2025Review
- Molecular and functional profiling of primary normal ovarian cells defines insights into cancer development and drug responses.Molecular therapy. Oncology · 2024Article
- Advances in ovarian tumor stem cells and therapy.Cell biochemistry and biophysics · 2024Review
- The prognostic value of MEK pathway-associated estrogen receptor signaling activity for female cancers.British journal of cancer · 2024Article
- Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises.Cancers · 2022Review
- Enhanced Therapeutic Effect of Optimized Melittin-dKLA, a Peptide Agent Targeting M2-like Tumor-Associated Macrophages in Triple-Negative Breast Cancer.International journal of molecular sciences · 2022Article
- Optimized Transcriptional Signature for Evaluation of MEK/ERK Pathway Baseline Activity and Long-Term Modulations in Ovarian Cancer.International journal of molecular sciences · 2022Article
- Applications of Proteomics in Ovarian Cancer: Dawn of a New Era.Proteomes · 2022Review
- Efficacy evaluation of multi-immunotherapy in ovarian cancer: From bench to bed.Frontiers in immunology · 2022Review
- Aberrant MAPK Signaling Offers Therapeutic Potential for Treatment of Ovarian Carcinoma.OncoTargets and therapy · 2022Review
- Four Types of RNA Modification Writer-Related lncRNAs Are Effective Predictors of Prognosis and Immunotherapy Response in Serous Ovarian Carcinoma.Frontiers in immunology · 2022Article
- MicroRNAs as the critical regulators of cisplatin resistance in gastric tumor cells.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2021Review
- Article
- Integrated molecular characterisation of the MAPK pathways in human cancers reveals pharmacologically vulnerable mutations and gene dependencies.Communications biology · 2021Article
- Oncogenic mutation in RAS-RAF axis leads to increased expression of GREB1, resulting in tumor proliferation in colorectal cancer.Cancer science · 2020Article
- Therapeutic efficacy of liposomal Grb2 antisense oligodeoxynucleotide (L-Grb2) in preclinical models of ovarian and uterine cancer.Oncotarget · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
purposeAlthough 67% of high-grade serous ovarian cancers (HGSOC) express the estrogen receptor (ER), most fail antiestrogen therapy. Because MAPK activation is frequent in ovarian cancer, we investigated if estrogen regulates MAPK and if MEK inhibition (MEKi) reverses antiestrogen resistance. EXPERIMENTAL
designEffects of MEKi (selumetinib), antiestrogen (fulvestrant), or both were assayed in ER-positive HGSOC in vitro and in xenografts. Response biomarkers were investigated by gene expression microarray and reverse phase protein array (RPPA). Genes differentially expressed in two independent primary HGSOC datasets with high versus low pMAPK by RPPA were used to generate a "MAPK-activated gene signature." Gene signature components that were reversed by MEKi were then identified.
resultsHigh intratumor pMAPK independently predicts decreased survival (HR, 1.7; CI > 95%,1.3-2.2; P = 0.0009) in 408 HGSOC from The Cancer Genome Atlas. A differentially expressed "MAPK-activated" gene subset was also prognostic. "MAPK-activated genes" in HGSOC differ from those in breast cancer. Combined MEK and ER blockade showed greater antitumor effects in xenografts than monotherapy. Gene set enrichment analysis and RPPA showed that dual therapy downregulated DNA replication and cell-cycle drivers, and upregulated lysosomal gene sets. Selumetinib reversed expression of a subset of "MAPK-activated genes" in vitro and/or in xenografts. Three of these genes were prognostic for poor survival (P = 0.000265) and warrant testing as a signature predictive of MEKi response.
conclusionsHigh pMAPK is independently prognostic and may underlie antiestrogen failure. Data support further evaluation of fulvestrant and selumetinib in ER-positive HGSOC. The MAPK-activated HGSOC signature may help identify MEK inhibitor responsive tumors.
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.