ArticleGynecologic oncology2014
Analyses of merlin/NF2 connection to FAK inhibitor responsiveness in serous ovarian cancer.
Article in Gynecologic oncology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- EANO guideline on the diagnosis and management of meningiomas.Neuro-oncology · 2021Guideline
- Nf2-FAK signaling axis is critical for cranial bone ossification and regeneration.Nature communications · 2025Article
- Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.Frontiers in oncology · 2025Review
- TNIK in disease: from molecular insights to therapeutic prospects.Apoptosis : an international journal on programmed cell death · 2024Review
- Drug target therapy and emerging clinical relevance of exosomes in meningeal tumors.Molecular and cellular biochemistry · 2024Review
- Novel Medical Therapies in Meningiomas.Advances in experimental medicine and biology · 2023Article
- Article
- Focal adhesion kinase priming in pancreatic cancer, altering biomechanics to improve chemotherapy.Biochemical Society transactions · 2022Article
- Clinical significance of metabolism-related genes and FAK activity in ovarian high-grade serous carcinoma.BMC cancer · 2022Article
- The Role of E-Cadherin and microRNA on FAK Inhibitor Response in Malignant Pleural Mesothelioma (MPM).International journal of molecular sciences · 2021Article
- Focal adhesion kinase inhibitor BI 853520 inhibits cell proliferation, migration and EMT process through PI3K/AKT/mTOR signaling pathway in ovarian cancer.Discover oncology · 2021Article
- Extracellular Matrices and Cancer-Associated Fibroblasts: Targets for Cancer Diagnosis and Therapy?Cancers · 2021Review
- Current experimental therapies for atypical and malignant meningiomas.Journal of neuro-oncology · 2021Review
- BRD4 modulates vulnerability of triple-negative breast cancer to targeting of integrin-dependent signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2020Article
- An update on the CNS manifestations of neurofibromatosis type 2.Acta neuropathologica · 2020Review
- T-cell co-stimulation in combination with targeting FAK drives enhanced anti-tumor immunity.eLife · 2020Article
- Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy.The FEBS journal · 2019Review
- Ovarian Cancer Stem Cells: Role in Metastasis and Opportunity for Therapeutic Targeting.Cancers · 2019Review
- Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins.Science signaling · 2019Article
- Titanium discs coated with 3,4-dihydroxy-l-phenylalanine promote osteogenic differentiation of human bone mesenchymal stem cellsRSC advances · 2019Article
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
objectiveFocal adhesion kinase (FAK) is overexpressed in serous ovarian cancer. Loss of merlin, a product of the neurofibromatosis 2 tumor suppressor gene, is being evaluated as a biomarker for FAK inhibitor sensitivity in mesothelioma. Connections between merlin and FAK in ovarian cancer remain undefined.
methodsNine human and two murine ovarian cancer cell lines were analyzed for growth in the presence of a small molecule FAK inhibitor (PF-271, also termed VS-6062) from 0.1 to 1 μM for 72 h. Merlin was evaluated by immunoblotting and immunostaining of a human ovarian tumor tissue array. Growth of cells was analyzed in an orthotopic tumor model and evaluated in vitro after stable shRNA-mediated merlin knockdown.
resultsGreater than 50% inhibition of OVCAR8, HEY, and ID8-IP ovarian carcinoma cell growth occurred with 0.1 μM PF-271 in anchorage-independent (p<0.001) but not in adherent culture conditions. PF-271-mediated reduction in FAK Y397 phosphorylation occurred independently of growth inhibition. Suspended growth of OVCAR3, OVCAR10, IGROV1, IGROV1-IP, SKOV3, SKOV3-IP, A2780, and 5009-MOVCAR was not affected by 0.1 μM PF-271. Merlin expression did not correlate with serous ovarian tumor grade or stage. PF-271 (30 mg/kg, BID) did not inhibit 5009-MOVCAR tumor growth and merlin knockdown in SKOV3-IP and OVCAR10 cells did not alter suspended cell growth upon PF-271 addition.
conclusionsDifferential responsiveness to FAK inhibitor treatment was observed. Intrinsic low merlin protein level correlated with PF-271-mediated anchorage-independent growth inhibition, but reduction in merlin expression did not induce sensitivity to FAK inhibition. Merlin levels may be useful for patient stratification in FAK inhibitor trials.
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