ArticleCancers2021
The MEK1/2 Pathway as a Therapeutic Target in High-Grade Serous Ovarian Carcinoma.
Article in Cancers, 2021. 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, 28 citations in OpenAlex.
- Lys-ing the Resistance: Targeting Lysosomes to Overcome Chemoresistance in Ovarian Cancer.Current oncology reports · 2026Review
- Functional genomics pipeline identifies CRL4 inhibition for the treatment of ovarian cancer.Clinical and translational medicine · 2025Article
- Gastric cancer patient withAME case reports · 2025Article
- Unveiling drug resistance pathways in high-grade serous ovarian cancer(HGSOC): recent advances and future perspectives.Frontiers in immunology · 2025Review
- Molecular and functional profiling of primary normal ovarian cells defines insights into cancer development and drug responses.Molecular therapy. Oncology · 2024Article
- Discovery of Trametinib as an orchestrator for cytoskeletal vimentin remodeling.Journal of molecular cell biology · 2024Article
- Targeted therapy in high grade serous ovarian Cancer: A literature review.Gynecologic oncology reports · 2024Review
- Pectin: Health-promoting properties as a natural galectin-3 inhibitor.Glycoconjugate journal · 2024Review
- Deguelin Restores Paclitaxel Sensitivity in Paclitaxel-Resistant Ovarian Cancer Cells via Inhibition of the EGFR Signaling Pathway.Cancer management and research · 2024Article
- High-grade serous ovarian carcinoma, the "Achiles' hill" for clinicians and molecular biologists: a molecular insight.Molecular biology reports · 2023Review
- Deciphering Common Traits of Breast and Ovarian Cancer Stem Cells and Possible Therapeutic Approaches.International journal of molecular sciences · 2023Review
- Blockage of retinoic acid signaling via RARγ suppressed the proliferation of pancreatic cancer cells by arresting the cell cycle progression of the G1-S phase.Cancer cell international · 2023Article
- Patient-Derived Organoids: The Beginning of a New Era in Ovarian Cancer Disease Modeling and Drug Sensitivity Testing.Biomedicines · 2022Review
- Kinase Inhibitors in the Treatment of Ovarian Cancer: Current State and Future Promises.Cancers · 2022Review
- Azelnidipine inhibits esophageal squamous cell carcinoma proliferationMolecular therapy oncolytics · 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
- Protein expression profiling identifies a prognostic model for ovarian cancer.BMC women's health · 2022Article
- Inhibition of MEK-ERK pathway enhances oncolytic vaccinia virus replication in doxorubicin-resistant ovarian cancer.Molecular therapy oncolytics · 2022Article
- Cryptocaryone Promotes ROS-Dependent Antiproliferation and Apoptosis in Ovarian Cancer Cells.Cells · 2022Article
- Preclinical Assessment of MEK Inhibitors for Malignant Peripheral Nerve Sheath Tumors Reveals Differences in Efficacy and Adaptive Response.Frontiers in oncology · 2022Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
High-grade serous ovarian carcinoma (HGSOC) is the deadliest of gynecological cancers due to its high recurrence rate and acquired chemoresistance. RAS/MEK/ERK pathway activation is linked to cell proliferation and therapeutic resistance, but the role of MEK1/2-ERK1/2 pathway in HGSOC is poorly investigated. We evaluated MEK1/2 pathway activity in clinical HGSOC samples and ovarian cancer cell lines using immunohistochemistry, immunoblotting, and RT-qPCR. HGSOC cell lines were used to assess immediate and lasting effects of MEK1/2 inhibition with trametinib in vitro. Trametinib effect on tumor growth in vivo was investigated using mouse xenografts. MEK1/2 pathway is hyperactivated in HGSOC and is further stimulated by cisplatin treatment. Trametinib treatment causes cell cycle arrest in G1/0-phase and reduces tumor growth rate in vivo but does not induce cell death or reduce fraction of CD133+ stem-like cells, while increasing expression of stemness-associated genes instead. Transient trametinib treatment causes long-term increase in a subpopulation of cells with high aldehyde dehydrogenase (ALDH)1 activity that can survive and grow in non-adherent conditions. We conclude that MEK1/2 inhibition may be a promising approach to suppress ovarian cancer growth as a maintenance therapy. Promotion of stem-like properties upon MEK1/2 inhibition suggests a possible mechanism of resistance, so a combination with CSC-targeting drugs should be considered.
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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.