{"doi":"10.3390/cancers13061369","title":"The MEK1/2 Pathway as a Therapeutic Target in High-Grade Serous Ovarian Carcinoma","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.","journal":"Cancers","year":2021,"id":169183,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":29,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9594,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":699515,"name":"Imran Khan","orcid":"0000-0001-9802-0429","position":1,"is_corresponding":false},{"id":700087,"name":"Yeonjung Park","orcid":null,"position":2,"is_corresponding":false},{"id":700088,"name":"Jessica Ezell","orcid":null,"position":3,"is_corresponding":false},{"id":247747,"name":"Geeta Mehta","orcid":"0000-0001-5967-6425","position":4,"is_corresponding":false},{"id":699516,"name":"Abdelrahman Yousif","orcid":"0000-0001-5329-8929","position":5,"is_corresponding":false},{"id":699517,"name":"Linda Hong","orcid":"0000-0003-1192-5861","position":6,"is_corresponding":false},{"id":247749,"name":"Ronald J. Buckanovich","orcid":"0000-0002-5665-9790","position":7,"is_corresponding":false},{"id":699518,"name":"Akimasa Takahashi","orcid":"0000-0001-5698-553X","position":8,"is_corresponding":false},{"id":699519,"name":"Ilana Chefetz","orcid":"0000-0001-6049-0513","position":9,"is_corresponding":false},{"id":699514,"name":"Mikhail S. Chesnokov","orcid":"0000-0001-8530-692X","position":0,"is_corresponding":true}],"reference_count":89,"raw_metadata":null,"created_at":"2026-07-18T23:46:11.334362Z","pmid":"33803586","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}