ArticleMolecular cancer therapeutics2012
MEK1/2 inhibitor selumetinib (AZD6244) inhibits growth of ovarian clear cell carcinoma in a PEA-15-dependent manner in a mouse xenograft model.
Article in Molecular cancer therapeutics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 27 citations in OpenAlex.
- Anoikis in cancer: molecular mechanisms, resistance, and therapeutic strategies.Apoptosis : an international journal on programmed cell death · 2026Review
- Carbon Dot-Enhanced Doxorubicin Liposomes: A Dual-Functional Nanoplatform for Cancer Therapy.International journal of molecular sciences · 2025Article
- Targeting USP8 causes synthetic lethality through degradation of FGFR2 in ARID1A-deficient ovarian clear cell carcinoma.NPJ precision oncology · 2025Article
- Identification of potential novel N6-methyladenosine effector-related lncRNA biomarkers for serous ovarian carcinoma: a machine learning-based exploration in the framework of 3P medicine.Frontiers in pharmacology · 2024Article
- Selumetinib: a selective MEK1 inhibitor for solid tumor treatment.Clinical and experimental medicine · 2023Review
- Mutations in the RAS/MAPK Pathway Drive Replication Repair-Deficient Hypermutated Tumors and Confer Sensitivity to MEK Inhibition.Cancer discovery · 2021Article
- Article
- Novel Small Molecule MEK Inhibitor URML-3881 Enhances Cisplatin Sensitivity in Clear Cell Ovarian Cancer.Translational oncology · 2019Article
- Anti-tumor and anti-metastasis efficacy of E6201, a MEK1 inhibitor, in preclinical models of triple-negative breast cancer.Breast cancer research and treatment · 2019Article
- Dual Src and MEK Inhibition Decreases Ovarian Cancer Growth and Targets Tumor Initiating Stem-Like Cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- Whole-genome sequencing revealed novel prognostic biomarkers and promising targets for therapy of ovarian clear cell carcinoma.British journal of cancer · 2017Article
- Histone Deacetylase Inhibitor Enhances the Efficacy of MEK Inhibitor through NOXA-Mediated MCL1 Degradation in Triple-Negative and Inflammatory Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2017Article
- 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
- On the Quest of Cellular Functions of PEA-15 and the Therapeutic Opportunities.Pharmaceuticals (Basel, Switzerland) · 2015Review
- Ovarian cancer: new developments in clear cell carcinoma and hopes for targeted therapy.Japanese journal of clinical oncology · 2015Review
- The promise and challenge of ovarian cancer models.Translational cancer research · 2015Article
- Xenotransplantation models to study the effects of toxicants on human fetal tissues.Birth defects research. Part B, Developmental and reproductive toxicology · 2014Review
- Article
- Dual HER/VEGF receptor targeting inhibits in vivo ovarian cancer tumor growth.Molecular cancer therapeutics · 2013Article
- Predicting time to ovarian carcinoma recurrence using protein markers.The Journal of clinical investigation · 2013Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
Clear cell carcinoma (CCC) of the ovary tends to show resistance to standard chemotherapy, which results in poor survival for patients with CCC. Developing a novel therapeutic strategy is imperative to improve patient prognosis. Epidermal growth factor receptor (EGFR) is frequently expressed in epithelial ovarian cancer. One of the major downstream targets of the EGFR signaling cascade is extracellular signal-related kinase (ERK). PEA-15, a 15-kDa phosphoprotein, can sequester ERK in the cytoplasm. MEK1/2 plays a central role in integrating mitogenic signals into the ERK pathway. We tested the hypothesis that inhibition of the EGFR-ERK pathway suppresses tumorigenicity in CCC, and we investigated the role of PEA-15 in ERK-targeted therapy in CCC. We screened a panel of 4 CCC cell lines (RMG-I, SMOV-2, OVTOKO, and KOC-7c) and observed that the EGFR tyrosine kinase inhibitor erlotinib inhibited cell proliferation of EGFR-overexpressing CCC cell lines through partial dependence on the MEK/ERK pathway. Furthermore, erlotinib-sensitive cell lines were also sensitive to the MEK inhibitor selumetinib (AZD6244), which is under clinical development. Knockdown of PEA-15 expression resulted in reversal of selumetinib-sensitive cells to resistant cells, implying that PEA-15 contributes to selumetinib sensitivity. Both selumetinib and erlotinib significantly suppressed tumor growth (P < 0.0001) in a CCC xenograft model. However, selumetinib was better tolerated; erlotinib-treated mice exhibited significant toxic effects (marked weight loss and severe skin peeling) at high doses. Our findings indicate that the MEK-ERK pathway is a potential target for EGFR-overexpressing CCC and indicate that selumetinib and erlotinib are worth exploring as therapeutic agents for CCC.
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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 Socratic graph.