ArticlePloS one2013
Exploiting MEK inhibitor-mediated activation of ERα for therapeutic intervention in ER-positive ovarian carcinoma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 16 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
16 citing papers in PubMed, 27 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
- Recent Advances (2020-2025) in Estrogen and ER-Positive Breast Cancer: Receptor Signaling, Tumor Microenvironment, Endocrine Therapy Resistance and Innovative Treatment Strategies-A Comprehensive Review.Cancer management and research · 2026Review
- Preclinical Efficacy of the Estrogen Receptor Degrader Fulvestrant in Combination with RAF/MEK Clamp Avutometinib and FAK Inhibitor in a Low-Grade Serous Ovarian Cancer Animal Model with Acquired Resistance to Chemotherapy and Aromatase Inhibitor.International journal of molecular sciences · 2025Article
- Novel Endocrine Therapeutic Opportunities for Estrogen Receptor-Positive Ovarian Cancer-What Can We Learn from Breast Cancer?Cancers · 2024Review
- Dual Fulvestrant-Trametinib Therapy in Recurrent Low-Grade Serous Ovarian Cancer.The oncologist · 2020Article
- LncRNA PVT1 epigenetically stabilizes and post-transcriptionally regulates FOXM1 by acting as a microRNA sponge and thus promotes malignant behaviors of ovarian cancer cells.American journal of translational research · 2020Article
- Possible Roles of Mitochondrial Dynamics and the Effects of Pharmacological Interventions in Chemoresistant Ovarian Cancer.EBioMedicine · 2018Review
- Active Estrogen Receptor-alpha Signaling in Ovarian Cancer Models and Clinical Specimens.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- Preclinical evaluation of radiation and systemic, RGD-targeted, adeno-associated virus phage-TNF gene therapy in a mouse model of spontaneously metastatic melanoma.Cancer gene therapy · 2017Article
- IL15 Agonists Overcome the Immunosuppressive Effects of MEK Inhibitors.Cancer research · 2016Article
- The RNA-binding protein LARP1 is a post-transcriptional regulator of survival and tumorigenesis in ovarian cancer.Nucleic acids research · 2016Article
- MAPK Activation Predicts Poor Outcome and the MEK Inhibitor, Selumetinib, Reverses Antiestrogen Resistance in ER-Positive High-Grade Serous Ovarian Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Correction: Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma.PloS one · 2016Article
- Review
- Estrogen signaling crosstalk: Implications for endocrine resistance in ovarian cancer.The Journal of steroid biochemistry and molecular biology · 2014Review
- ERK/MAPK regulates ERRγ expression, transcriptional activity and receptor-mediated tamoxifen resistance in ER+ breast cancer.The FEBS journal · 2014Article
Corrections and comments
- Erratum issuedCorrection: Exploiting MEK Inhibitor-Mediated Activation of ERα for Therapeutic Intervention in ER-Positive Ovarian Carcinoma.2016 · Samaweera, Leleesha [corrected to Samaraweera, Leleesha]
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
While the clinical benefit of MEK inhibitor (MEKi)-based therapy is well established in Raf mutant malignancies, its utility as a suppressor of hyperactive MAPK signaling in the absence of mutated Raf or Ras, is an area of ongoing research. MAPK activation is associated with loss of ERα expression and hormonal resistance in numerous malignancies. Herein, we demonstrate that MEKi induces a feedback response that results in ERα overexpression, phosphorylation and transcriptional activation of ER-regulated genes. Mechanistically, MEKi-mediated ERα overexpression is largely independent of erbB2 and AKT feedback activation, but is ERK-dependent. We subsequently exploit this phenomenon therapeutically by combining the ER-antagonist, fulvestrant with MEKi. This results in synergistic suppression of tumor growth, in vitro and potentiation of single agent activity in vivo in nude mice bearing xenografts. Thus, we demonstrate that exploiting adaptive feedback after MEKi can be used to sensitize ERα-positive tumors to hormonal therapy, and propose that this strategy may have broader clinical utility in ERα-positive ovarian carcinoma.
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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.