ArticleCancer cell2018
Targeting PKCδ as a Therapeutic Strategy against Heterogeneous Mechanisms of EGFR Inhibitor Resistance in EGFR-Mutant Lung Cancer.
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Article in Cancer cell, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers, 1 of them a synthesis that pooled it.
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46citing papers in PubMed, 1 pooled it
5.9field-weighted citation impact, top 3% of its field
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Who cites it
46 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- Pooled it
- Research on the correlation and potential mechanism of PKCδ expression with efficacy and prognosis in diffuse large B-cell lymphoma.Frontiers in oncology · 2026Article
- Prolonging lung cancer response to EGFR inhibition by targeting the selective advantage of resistant cells.Nature communications · 2025Article
- Anti-galectin-9 therapy synergizes with EGFR inhibition to reprogram the tumor microenvironment and overcome immune evasion.Journal for immunotherapy of cancer · 2025Article
- Article
- Modulation of tumor inflammatory signaling and drug sensitivity by CMTM4.The EMBO journal · 2025Article
- Targeting PKC as a Therapeutic Strategy to Overcome Chemoresistance in TNBC by Restoring Aurora Kinase B Expression.Journal of cellular and molecular medicine · 2025Article
- Signaling dynamics in coexisting monoclonal cell subpopulations unveil mechanisms of resistance to anti-cancer compounds.Cell communication and signaling : CCS · 2024Article
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.International journal of molecular sciences · 2023Review
- RAIDS atlas of significant genetic and protein biomarkers in cervical cancer.Journal of gynecologic oncology · 2023Review
- Inhibition of protein kinase C delta leads to cellular senescence to induce anti-tumor effects in colorectal cancer.Cancer science · 2023Article
- Highly Mimetic Ex Vivo Lung-Cancer Spheroid-Based Physiological Model for Clinical Precision Therapeutics.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Article
- Nuclear export signal mutation of epidermal growth factor receptor enhances malignant phenotypes of cancer cells.American journal of cancer research · 2023Article
- Development of triazole-based PKC-inhibitors to overcome resistance to EGFR inhibitors in EGFR-mutant lung cancers.American journal of cancer research · 2023Article
- Tumor PKCδ instigates immune exclusion in EGFR-mutated non-small cell lung cancer.BMC medicine · 2022Article
- A Genomically and Clinically Annotated Patient-Derived Xenograft Resource for Preclinical Research in Non-Small Cell Lung Cancer.Cancer research · 2022Article
- Protein Kinase C (PKC) Isozymes as Diagnostic and Prognostic Biomarkers and Therapeutic Targets for Cancer.Cancers · 2022Review
- Targeting the ALK-CDK9-Tyr19 kinase cascade sensitizes ovarian and breast tumors to PARP inhibition via destabilization of the P-TEFb complex.Nature cancer · 2022Article
- Protein tyrosine kinase inhibitor resistance in malignant tumors: molecular mechanisms and future perspective.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
35 authors at 6 institutions in 3 countries.
Pei-Chih LeeDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yueh-Fu FangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Thoracic Medicine, Chang Gung Foundation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; Department of Pulmonary and Critical Care Medicine Saint Paul's Hospital, Taoyuan City 33069, Taiwan; College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Hirohito YamaguchiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wei-Jan WangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Tse-Ching ChenCollege of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Pathology, Chang Gung Foundation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
Xuan HongDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Thoracic Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang 150081, China.
Baozhen KeDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Weiya XiaDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yongkun WeiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Zhengyu ZhaDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yan WangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Han-Pin KuoDepartment of Thoracic Medicine, Chang Gung Foundation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan; College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.
Chih-Wei WangCollege of Medicine, Chang Gung University, Taoyuan 333, Taiwan; Department of Pathology, Chang Gung Foundation, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan.
Chih-Yen TuDivision of Pulmonary and Critical Care Medicine, China Medical University and Hospital, Taichung 404, Taiwan; Department of Internal Medicine, China Medical University and Hospital, Taichung 404, Taiwan; School of Medicine, China Medical University, Taichung 404, Taiwan; Department of Life Science, National Chung-Hsing University, Taichung 402, Taiwan.
Chia-Hung ChenDivision of Pulmonary and Critical Care Medicine, China Medical University and Hospital, Taichung 404, Taiwan; Department of Internal Medicine, China Medical University and Hospital, Taichung 404, Taiwan; Department of Respiratory Therapy, China Medical University, Taichung 404, Taiwan; Graduate Institute of Clinical Medical Science, China Medical University, Taichung 404, Taiwan.
Wei-Chien HuangCenter for Molecular Medicine and Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
Shu-Fen ChiangCancer Center, China Medical University, Taichung 404, Taiwan.
Lei NieDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Junwei HouDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Chun-Te ChenDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Longfei HuoDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Wen-Hao YangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Rong DengDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
Katsuya NakaiDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Yi-Hsin HsuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Shih-Shin ChangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Tai-Jan ChiuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Department of Medical Oncology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 333, Taiwan.
Jun TangDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou 510060, China.
Ran ZhangDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Li WangDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Bingliang FangDepartment of Thoracic and Cardiovascular Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Ting ChenDivision of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Kwok-Kin WongDivision of Hematology & Medical Oncology, Laura and Isaac Perlmutter Cancer Center, New York University Langone Medical Center, New York, NY 10016, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Belfer Center for Applied Cancer Science, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Jennifer L HsuDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan.
Mien-Chie HungDepartment of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA; Center for Molecular Medicine and Graduate Institute of Biomedical Sciences, China Medical University, Taichung 404, Taiwan; Department of Biotechnology, Asia University, Taichung 413, Taiwan. Electronic address: mhung@mdanderson.org.
The University of Texas MD Anderson Cancer Center · USChang Gung University · TWAsia University · TWChina Medical University · TWNational Chung Hsing University · TWNYU Langone Health · US
Funding
Tumor Evolution and Metastasis ProgramP30CA016672 · NCI · UNIVERSITY OF TX MD ANDERSON CAN CTR · PI Fabien Delerue · 1985 to 2026
$290.8MNCI NIH HHS P30 CA016672
Abstract
Multiple mechanisms of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have been identified in EGFR-mutant non-small cell lung cancer (NSCLC); however, recurrent resistance to EGFR TKIs due to the heterogeneous mechanisms underlying resistance within a single patient remains a major challenge in the clinic. Here, we report a role of nuclear protein kinase Cδ (PKCδ) as a common axis across multiple known TKI-resistance mechanisms. Specifically, we demonstrate that TKI-inactivated EGFR dimerizes with other membrane receptors implicated in TKI resistance to promote PKCδ nuclear translocation. Moreover, the level of nuclear PKCδ is associated with TKI response in patients. The combined inhibition of PKCδ and EGFR induces marked regression of resistant NSCLC tumors with EGFR mutations.
Indexed as
AdultAgedAged, 80 and overCarcinoma, Non-Small-Cell LungCell Line, TumorCell NucleusCell SurvivalDrug Resistance, NeoplasmErbB ReceptorsFemaleHumansLung NeoplasmsMaleMicroscopy, ConfocalMiddle AgedMolecular Targeted TherapyEGFR protein, humanErbB ReceptorsProtein Kinase C-deltaProtein Kinase InhibitorsEGFRheterogeneityheterogeneous mechanism of TKI resistanceheterogeneous resistancelung cancerPKC deltaPKCδresistanceTKItyrosine kinase inhibitor
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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.