ArticleNature genetics2015
The Hippo effector YAP promotes resistance to RAF- and MEK-targeted cancer therapies.
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Article in Nature genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 355 papers.
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355citing papers in PubMed
28.2field-weighted citation impact, top 1% of its field
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Who cites it
355 citing papers in PubMed, 552 citations in OpenAlex.
- YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial.Nature medicine · 2025Trial
- Trial
- Yap1 Mediates Trametinib Resistance in Head and Neck Squamous Cell Carcinomas.Clinical cancer research : an official journal of the American Association for Cancer Research · 2021Trial
- Oncogenic RAS as an adaptive signaling ecosystem: context-dependent vulnerabilities and resistance-informed therapeutic design.Experimental hematology & oncology · 2026Review
- Lineage identity governs oncogene dependence in mouse NSCLC models of KRAS inhibitor resistance.Nature genetics · 2026Article
- Extracellular matrix reprogramming by the YAP/TAZ/TGF-β2 axis drives immune exclusion in cholangiocarcinoma models.The Journal of clinical investigation · 2026Article
- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Genome-Wide CRISPR Screen Identifies a microRNA Orchestrating Pleiotropic Resistance to Targeted Therapy and T Cell Immunity in Melanoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Covalent pan-TEAD inhibitors block YAP activity and demonstrate brain penetrance in a Hippo-dependent cancer model.Nature communications · 2026Article
- Basroparib inhibits YAP-driven cancers by stabilizing angiomotin.Molecular oncology · 2026Article
- Research on the Hippo Pathway in Cancer.Cells · 2026Review
- Enhancing gastric cancer immunotherapy: Insights from multi-omics analysis and innovations in photodynamic-chemotherapy nanoplatforms.Cell reports. Medicine · 2026Article
- OSBPL3 drives colorectal cancer progression via Hippo-YAP signaling and modulates MEK inhibitor sensitivity.Communications biology · 2026Article
- High-effect synergy from dual HDAC6 and YAP-TEAD inhibition in ovarian clear cell carcinoma.Cancer cell international · 2026Article
- Pancreatic cancer: molecular pathogenesis and emerging therapeutic strategies.Signal transduction and targeted therapy · 2026Review
- Honokiol Suppresses Stemness and Sensitizes Triple-Negative Breast Cancer to Chemotherapy via YAP/TAZ-TEAD Inhibition.Oncology research · 2026Article
- TEAD inhibitors synergize with MEK, SHP2 and mTOR inhibitors in NF1 and NF2 cell lines.microPublication biology · 2026Article
- TEAD inhibitors re-sensitize drug-resistant NF1 MPNST cells to MEK inhibitors.microPublication biology · 2026Article
- Experimental assessment of computationally nominated small molecules targeting the YAP-TEAD interface in Hippo pathway-altered mesothelioma cell models.Frontiers in oncology · 2026Article
- Targeting TAZ-TEAD in minimal residual disease enhances the duration of targeted therapy in melanoma models.Nature communications · 2025Article
295 more citing papers are in PubMed but not listed here.
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Authors and funding
33 authors at 9 institutions in 3 countries.
Luping Lin1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Amit J Sabnis1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA. [3] Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of California, San Francisco, San Francisco, California, USA.
Elton Chan1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Victor Olivas1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Lindsay Cade1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Evangelos Pazarentzos1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.ORCID 0000000254531646
Saurabh Asthana1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Dana Neel1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Jenny Jiacheng Yan1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Xinyuan Lu1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Luu Pham1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Mingxue M Wang1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Niki KarachaliouCancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Maria Gonzalez CaoCancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Jose Luis ManzanoMedical Oncology Service, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Jose Luis RamirezTranslational Oncology Laboratory, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Fundació Institut Recerca Germans Trias i Pujol (IGTP), Barcelona, Spain.
Jose Miguel Sanchez TorresMedical Oncology Service, Hospital Universitario de La Princesa, Madrid, Spain.
Fiamma ButtittaCenter for Predictive Molecular Medicine, University Foundation, Chieti-Pescara, Chieti, Italy.
Charles M Rudin1] Molecular Chemistry and Pharmacology Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA. [2] Thoracic Oncology Service, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Eric A Collisson1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Alain Algazi1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Eric RobinsonRonald O. Perelman Department of Dermatology, Medicine and Urology, New York University Cancer Institute, New York, New York, USA.
Iman OsmanRonald O. Perelman Department of Dermatology, Medicine and Urology, New York University Cancer Institute, New York, New York, USA.
Eva Muñoz-CouseloVall d'Hebron Institute of Oncology, Barcelona, Spain.
Javier CortesVall d'Hebron Institute of Oncology, Barcelona, Spain.
Dennie T Frederick1] Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Massachusetts General Hospital Comprehensive Cancer Center, Boston, Massachusetts, USA.
Zachary A Cooper1] Department of Surgical Oncology, MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Genomic Medicine, MD Anderson Cancer Center, Houston, Texas, USA.
Martin McMahonHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
Antonio MarchettiCenter for Predictive Molecular Medicine, University Foundation, Chieti-Pescara, Chieti, Italy.
Rafael RosellCancer Biology and Precision Medicine Program, Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain.
Keith T Flaherty1] Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA. [2] Massachusetts General Hospital Comprehensive Cancer Center, Boston, Massachusetts, USA.
Jennifer A Wargo1] Department of Surgical Oncology, MD Anderson Cancer Center, Houston, Texas, USA. [2] Department of Genomic Medicine, MD Anderson Cancer Center, Houston, Texas, USA.
Trever G Bivona1] Department of Medicine, University of California, San Francisco, San Francisco, California, USA. [2] Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California, USA.
University of California, San Francisco · USInstitut Català d'Oncologia · ESMassachusetts General Hospital · USNew York University · USThe University of Texas MD Anderson Cancer Center · USUniversity of Chieti-Pescara · ITVall d'Hebron Institute of Oncology · ESHospital Universitario de La Princesa · ESMemorial Sloan Kettering Cancer Center · US
Funding
X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI Nicholas D Socci · 1985 to 2026
$347.4MTumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Scott Kopetz · 1985 to 2026
$290.8MTranscriptional mechanisms and melanomaP01CA163222 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Liu · 2013 to 2026
$25.3MStudying the initiation, progression and therapy of lung cancer in mouse modelsR01CA131261 · NCI · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI MARTIN MCMAHON · 2009 to 2026
$5.3MDiscovery of Rational Companion Therapeutic Targets to Optimize Cancer TreatmentDP2CA174497 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2012 to 2012
$2.3MHoward Hughes Medical InstituteNCI NIH HHS DP2 CA174497NCI NIH HHS DP2CA174497NCI NIH HHS P01 CA163222NCI NIH HHS P30 CA008748NCI NIH HHS R01 CA131261NCI NIH HHS R01CA131261
Abstract
Resistance to RAF- and MEK-targeted therapy is a major clinical challenge. RAF and MEK inhibitors are initially but only transiently effective in some but not all patients with BRAF gene mutation and are largely ineffective in those with RAS gene mutation because of resistance. Through a genetic screen in BRAF-mutant tumor cells, we show that the Hippo pathway effector YAP (encoded by YAP1) acts as a parallel survival input to promote resistance to RAF and MEK inhibitor therapy. Combined YAP and RAF or MEK inhibition was synthetically lethal not only in several BRAF-mutant tumor types but also in RAS-mutant tumors. Increased YAP in tumors harboring BRAF V600E was a biomarker of worse initial response to RAF and MEK inhibition in patients, establishing the clinical relevance of our findings. Our data identify YAP as a new mechanism of resistance to RAF- and MEK-targeted therapy. The findings unveil the synthetic lethality of combined suppression of YAP and RAF or MEK as a promising strategy to enhance treatment response and patient survival.
Indexed as
Adaptor Proteins, Signal TransducingAnimalsBiomarkers, TumorCell Line, TumorDrug Resistance, NeoplasmFemaleGene Knockdown TechniquesGenes, rasHEK293 CellsHeterograftsHippo Signaling PathwayHT29 CellsHumansMAP Kinase Kinase KinasesMAP Kinase Signaling SystemMiceAdaptor Proteins, Signal TransducingBiomarkers, TumorBRAF protein, humanMAP Kinase Kinase KinasesPhosphoproteinsProtein Kinase InhibitorsProtein Serine-Threonine KinasesProto-Oncogene Proteins B-rafTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins
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