ArticleNature communications2024
Focal adhesion kinase-YAP signaling axis drives drug-tolerant persister cells and residual disease in lung cancer.
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Article in Nature communications, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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75citing papers in PubMed
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Who cites it
75 citing papers in PubMed.
- YAP/TEAD inhibitor VT3989 in solid tumors: a phase 1/2 trial.Nature medicine · 2025Trial
- Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor-Mutated Non-Small Cell Lung Cancer: A Phase II Multicenter Study.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2024Trial
- Engineering microRNAs as multimodal cancer therapeutics.Molecular therapy. Nucleic acids · 2026Article
- Combined FAK and MEK inhibition suppresses chromosome 8 gain malignant peripheral nerve sheath tumors.The Journal of clinical investigation · 2026Article
- Functional genomic screens uncover FERMT2 as a critical regulator of YAP/TAZ-driven tumorigenicity.Cell death and differentiation · 2026Article
- Three decades of anaplastic lymphoma kinase: from physiological roles to cancer and immune evasion.Cancer metastasis reviews · 2026Review
- Dysregulated ITGA3/FAK/YAP axis mediates impaired alveolar type II epithelial cells function in COPD.Journal of advanced research · 2026Article
- Early EGFR Inhibition Triggers Actionable Tumor and Microenvironmental Remodeling in Lung Cancer.Cancer research communications · 2026Article
- AXL phosphosite mapping links FAK1 and YAP1 signaling to erlotinib resistance in EGFR-mutant lung cancer.Cell reports · 2026Article
- Plasticity of Non-Apoptotic Residual Tumor Cells After Neoadjuvant Immunochemotherapy: Epigenetic and Microenvironmental Determinants.Biomolecules · 2026Review
- Multidrug resistance in cancer: current understandings and future perspective.Molecular biomedicine · 2026Review
- Drug resistant cancer cells show increased nuclear mechanotransduction and mechanically targetable YAP-regulated vulnerability.Biomaterials · 2026Article
- RPRD1A drives lenvatinib resistance in hepatocellular carcinoma via the ITGA5-FAK signaling axis.Molecular biomedicine · 2026Article
- An EGFR co-amplified lncRNA HELDR promotes glioblastoma malignancy through KAT7-driven gene programs.Nature cell biology · 2026Article
- Review
- Liquid-liquid phase separation in cancer therapy resistance.iScience · 2026Review
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Tyrosine phosphoproteome profiling identifies cell-intrinsic signals limiting the efficacy of tyrosine kinase inhibitor therapies.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Propionate metabolism is dysregulated in non-small cell lung cancer patients and EGFR-mutant drug-tolerant persister cells.Scientific reports · 2026Article
15 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
35 authors.
Franziska Haderk *Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9658-2778
Yu-Ting Chou *Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Lauren Cech *Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-3621-4129
Celia Fernández-MéndezInstituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científícas (CSIC) y Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.ORCID http://orcid.org/0000-0001-8593-5507
Johnny YuHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Victor OlivasDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Ismail M MerazDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0001-9109-5196
Dora Barbosa RabagoDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
D Lucas KerrDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-0557-8341
Carlos GomezDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
David V AllegakoenDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Juan GuanDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
Khyati N ShahHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.
Kari A HerringtonCenter for Advanced Light Microscopy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4925-8072
Oghenekevwe M GbenedioDepartment of Anatomy, University of California, San Francisco, San Francisco, CA, USA.
Shigeki NanjoDivision of Medical Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan.ORCID http://orcid.org/0000-0001-8356-9849
Mourad MajidiDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
Whitney TamakiDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-1124-628X
Yashar K PourmoghadamDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Julia K RotowLowe Center for Thoracic Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Caroline E McCoachDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.
Jonathan W RiessUniversity of California Davis Comprehensive Cancer Center, Sacramento, CA, USA.ORCID http://orcid.org/0000-0001-7370-7304
J Silvio GutkindMoores Cancer Center, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5150-4482
Tracy T TangVivace Therapeutics, Inc., 1500 Fashion Island Blvd., Suite 102, San Mateo, CA, USA.
Leonard PostVivace Therapeutics, Inc., 1500 Fashion Island Blvd., Suite 102, San Mateo, CA, USA.
Bo HuangDepartment of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1704-4141
Pilar SantistebanInstituto de Investigaciones Biomédicas "Alberto Sols", Consejo Superior de Investigaciones Científícas (CSIC) y Universidad Autónoma de Madrid (UAM), Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Instituto de Salud Carlos III (ISCIII), Madrid, Spain.ORCID http://orcid.org/0000-0002-2758-796X
Hani GoodarziHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-9648-8949
Sourav BandyopadhyayHelen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-3120-923X
Calvin J KuoDepartment of Medicine, Division of Hematology, Stanford University School of Medicine, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-7427-5985
Jeroen P RooseDepartment of Anatomy, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-4746-2811
Wei WuDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6556-067X
Collin M BlakelyDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-8134-3651
Jack A RothDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.ORCID http://orcid.org/0000-0002-8955-1313
Trever G BivonaDepartment of Medicine, University of California, San Francisco, San Francisco, CA, USA. trever.bivona@ucsf.edu.ORCID http://orcid.org/0000-0001-5734-4128
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MStaff InvestigatorsP30CA093373 · NCI · UNIVERSITY OF CALIFORNIA DAVIS · PI Gina M Dayton · 2002 to 2026
$84.9MUNIVERSITY OF TEXAS--SPORE IN LUNG CANCERP50CA070907 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HEYMACH, JOHN V., MINNA, JOHN D. · 1996 to 2024
$57.4MUnderstand the metabolic fitness of naïve T cellsP01AI091580 · NIAID · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2011 to 2026
$31.1MUCSF Project 1U54CA224081 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona, Jack Roth · 2017 to 2026
$12.9MUniversity of Texas PDX Development and Trial CenterU54CA224065 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI DAMODARAN, SENTHILKUMAR, MERIC-BERNSTAM, FUNDA · 2017 to 2022
$7.7MThe Cancer Target Discovery and Development Network at UCSFU01CA217882 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BANDYOPADHYAY, SOURAV, BIVONA, TREVER G · 2017 to 2021
$5.2MOrganoid-based Discovery of Oncogenic Drivers and Treatment Resistance MechanismsU01CA217851 · NCI · STANFORD UNIVERSITY · PI CURTIS, CHRISTINA N, JI, HANLEE P · 2017 to 2021
$4.7MBalanced signaling cues to guide cell transitions in the blood lineage continuumR01HL120724 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI CHAKRABORTY, ARUP K., NOLAN, GARRY P · 2015 to 2019
$3.7MCharacterization of YAP as a rational companion target in lung cancerR01CA204302 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Trever G Bivona · 2017 to 2026
$3.7MMolecular understanding of leukemic bone marrow cytokine-Ras signals and metabolic dependenceR01CA187318 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI JEROEN ROOSE · 2015 to 2026
$3.6MRational Combined Inhibition of NF-kB and EGFR to Optimize Lung Cancer TreatmentR01CA169338 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI BIVONA, TREVER G · 2013 to 2023
$3.4MNCI NIH HHS P30 CA016672NCI NIH HHS P30 CA093373NCI NIH HHS P50 CA070907NCI NIH HHS R01 CA169338NCI NIH HHS R01 CA187318NCI NIH HHS R01 CA204302NCI NIH HHS R01 CA211052NCI NIH HHS R01 CA231300NCI NIH HHS R01 CA238236NCI NIH HHS R01 CA247551NCI NIH HHS U01 CA217851NCI NIH HHS U01 CA217882NCI NIH HHS U54 CA224065NCI NIH HHS U54 CA224081NHLBI NIH HHS R01 HL120724NIAID NIH HHS P01 AI091580NIAID NIH HHS R01 AI104789NIGMS NIH HHS R01 GM131641
Abstract
Targeted therapy is effective in many tumor types including lung cancer, the leading cause of cancer mortality. Paradigm defining examples are targeted therapies directed against non-small cell lung cancer (NSCLC) subtypes with oncogenic alterations in EGFR, ALK and KRAS. The success of targeted therapy is limited by drug-tolerant persister cells (DTPs) which withstand and adapt to treatment and comprise the residual disease state that is typical during treatment with clinical targeted therapies. Here, we integrate studies in patient-derived and immunocompetent lung cancer models and clinical specimens obtained from patients on targeted therapy to uncover a focal adhesion kinase (FAK)-YAP signaling axis that promotes residual disease during oncogenic EGFR-, ALK-, and KRAS-targeted therapies. FAK-YAP signaling inhibition combined with the primary targeted therapy suppressed residual drug-tolerant cells and enhanced tumor responses. This study unveils a FAK-YAP signaling module that promotes residual disease in lung cancer and mechanism-based therapeutic strategies to improve tumor response.
Indexed as
Carcinoma, Non-Small-Cell LungDrug Resistance, NeoplasmLung NeoplasmsSignal TransductionTranscription FactorsYAP-Signaling ProteinsAdaptor Proteins, Signal TransducingAnaplastic Lymphoma KinaseAnimalsAntineoplastic AgentsCell Line, TumorErbB ReceptorsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesHumansMiceAdaptor Proteins, Signal TransducingALK protein, humanAnaplastic Lymphoma KinaseAntineoplastic AgentsEGFR protein, humanErbB ReceptorsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesKRAS protein, humanProto-Oncogene Proteins p21(ras)PTK2 protein, humanTranscription FactorsYAP1 protein, humanYAP-Signaling Proteins
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