ArticleScience translational medicine2014
Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship.
Article in Science translational medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 152 papers.
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Who cites it
152 citing papers in PubMed, 243 citations in OpenAlex.
- Alliance A071401: Phase II Trial of Focal Adhesion Kinase Inhibition in Meningiomas With SomaticJournal of clinical oncology : official journal of the American Society of Clinical Oncology · 2023Trial
- BAP1 and USP1 cooperate to regulate FANCD2 stability and cell proliferation in mesothelioma cells.Cell death & disease · 2026Article
- Article
- Inhibition of focal adhesion kinase impairs tumor formation and preserves hearing in a murine model of NF2-related schwannomatosis.Science advances · 2026Article
- Strategic selection of MDM2 inhibitors enhances the efficacy of FAK inhibition in mesothelioma based on TP53 genotype.PloS one · 2026Article
- Epithelioid Mesothelioma Cells Exhibit Increased Ferroptosis Sensitivity Compared to Non-Epithelioid Mesothelioma Cells.Cancers · 2025Article
- Characterization of the extrinsic and intrinsic signatures and therapeutic vulnerability of small cell lung cancers.Signal transduction and targeted therapy · 2025Article
- Cardiomyocyte regeneration after infarction: changes, opportunities and challenges.Molecular and cellular biochemistry · 2025Review
- Transcriptional landscape of pleural mesothelioma patients in relation to NF2 gene mutational status.Journal of the Egyptian National Cancer Institute · 2025Article
- Mechanisms and Therapeutic Strategies for Minority Cell-Induced Paclitaxel Resistance and Tumor Progression Mediated by Mechanical Forces.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Molecular Mechanisms of Tumor Progression and Novel Therapeutic and Diagnostic Strategies in Mesothelioma.International journal of molecular sciences · 2025Review
- Nf2-FAK signaling axis is critical for cranial bone ossification and regeneration.Nature communications · 2025Article
- Combined inhibition of focal adhesion kinase and RAF/MEK elicits synergistic inhibition of melanoma growth and reduces metastases.Cell reports. Medicine · 2025Article
- Case Report: Advanced grade 2 meningioma withFrontiers in oncology · 2025Article
- Therapeutic Strategies to Improve the Treatment of Pleural Mesothelioma.Current medicinal chemistry · 2025Review
- Context-specific targeting of focal adhesion kinase in brain tumors: lessons from glioblastoma and neurofibromatosis type 2-mutant meningioma.Frontiers in oncology · 2025Review
- Meningioma: International Consortium on Meningiomas consensus review on scientific advances and treatment paradigms for clinicians, researchers, and patients.Neuro-oncology · 2024Review
- Effect of Different Glucose Levels and Glycation on Meningioma Cell Migration and Invasion.International journal of molecular sciences · 2024Article
- Synergistic effects of combined BET and FAK inhibition against Vestibular Schwannomas in NF2-related Schwannomatosis.Oncogene · 2024Article
- Preclinical evaluation of avutometinib and defactinib in high-grade endometrioid endometrial cancer.Cancer medicine · 2024Article
92 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
The goal of targeted therapy is to match a selective drug with a genetic lesion that predicts for drug sensitivity. In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin. Merlin expression is often lost in malignant pleural mesothelioma (MPM), an asbestos-induced aggressive cancer with limited treatment options. Our data demonstrate that low Merlin expression predicts for increased sensitivity of MPM cells to a FAK inhibitor, VS-4718, in vitro and in tumor xenograft models. Disruption of MPM cell-cell or cell-extracellular matrix (ECM) contacts with blocking antibodies suggests that weak cell-cell adhesions in Merlin-negative MPM cells underlie their greater dependence on cell-ECM-induced FAK signaling. This provides one explanation of why Merlin-negative cells are vulnerable to FAK inhibitor treatment. Furthermore, we validated aldehyde dehydrogenase as a marker of cancer stem cells (CSCs) in MPM, a cell population thought to mediate tumor relapse after chemotherapy. Whereas pemetrexed and cisplatin, standard-of-care agents for MPM, enrich for CSCs, FAK inhibitor treatment preferentially eliminates these cells. These preclinical results provide the rationale for a clinical trial in MPM patients using a FAK inhibitor as a single agent after first-line chemotherapy. With this design, the FAK inhibitor could potentially induce a more durable clinical response through reduction of CSCs along with a strong antitumor effect. Furthermore, our data suggest that patients with Merlin-negative tumors may especially benefit from FAK inhibitor treatment.
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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.