ArticleCancer cell2019
Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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71citing papers in PubMed
7.5field-weighted citation impact, top 2% of its field
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Who cites it
71 citing papers in PubMed, 118 citations in OpenAlex.
- Oncogenic EGFR rewires STING-TBK1 signalosomes to license DNA damage tolerance in NSCLC.The EMBO journal · 2026Article
- RASD2 Drives Renal Clear Cell Carcinoma Progression via RAF1 (Ser338) Phosphorylation.Cancer science · 2026Article
- CAF-derived PAI-1 serves as an EGFR ligand and fuels KRAS-mutant pancreatic cancer.Nature communications · 2026Article
- A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Integrating computational chemistry and machine learning to predict KRAS mutation-induced resistance.bioRxiv : the preprint server for biology · 2026Article
- A Transgenic mouse tolerant to syngeneic cancer cells expressing truncated human epidermal growth factor receptor.PloS one · 2026Article
- HDAC1 Regulates Acquired Resistance to EGFR Inhibitors through the TFCP2-NDRG1 Signaling Axis in Pancreatic Cancer.International journal of biological sciences · 2026Article
- RAF1 as a standalone therapeutic target in KRAS-driven lung adenocarcinoma: No added efficacy from co-targeting ARAF, EGFR, or DDR1.PloS one · 2026Article
- Article
- EGFR-targeted affibody-polyIC polyplex kills EGFR-overexpressing cancer cells without activating the EGFR.PloS one · 2026Article
- A targeted combination therapy achieves effective pancreatic cancer regression and prevents tumor resistance.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation.Nature communications · 2025Article
- KRAS: the Achilles' heel of pancreas cancer biology.The Journal of clinical investigation · 2025Review
- Pancreatic Cancer: Pathogenesis and Clinical Studies.MedComm · 2025Review
- Quantitative Live Imaging Reveals Phase Dependency of PDAC Patient-Derived Organoids on ERK and AMPK Activity.Cancer science · 2025Article
- Leveraging CAR macrophages targeting c-Met for precision immunotherapy in pancreatic cancer: insights from single-cell multi-omics.Molecular medicine (Cambridge, Mass.) · 2024Article
- Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth.Cancer discovery · 2024Article
- Novel RAF-directed approaches to overcome current clinical limits and block the RAS/RAF node.Molecular oncology · 2024Review
- Disruption of the pro-oncogenic c-RAF-PDE8A complex represents a differentiated approach to treating KRAS-c-RAF dependent PDAC.Scientific reports · 2024Article
- Cannabigerol Induces Autophagic Cell Death by Inhibiting EGFR-RAS Pathways in Human Pancreatic Ductal Adenocarcinoma Cell Lines.International journal of molecular sciences · 2024Article
11 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
29 authors at 7 institutions in 3 countries.
María Teresa BlascoMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Carolina NavasMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Guillermo Martín-SerranoBioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Osvaldo Graña-CastroBioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Carmen G LechugaMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Laura Martín-DíazMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Magdolna DjurecMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Jing LiMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Lucia Morales-CachoMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Laura Esteban-BurgosMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Javier Perales-PatónBioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Emilie Bousquet-MurMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Eva CastellanoMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Harrys K C JacobMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Lavinia CabrasMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Monica MusteanuMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Matthias DrostenMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain.
Sagrario OrtegaTransgenic Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Francisca MuleroMolecular Imaging Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Bruno SainzInstituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain; Department of Biochemistry, School of Medicine, Autonomous University of Madrid, 28018 Madrid, Spain.
Nelson DusettiCentre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR 7258, Aix-Marseille Université et Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163, Avenue de Luminy, 13288 Marseille, France.
Juan IovannaCentre de Recherche en Cancérologie de Marseille (CRCM), Inserm U1068, CNRS UMR 7258, Aix-Marseille Université et Institut Paoli-Calmettes, Parc Scientifique et Technologique de Luminy, 163, Avenue de Luminy, 13288 Marseille, France.
Francisco Sánchez-BuenoDepartment of Surgery, Clinical University Hospital 'Virgen Arrixaca' - Murcian Institute of Biomedical Investigation (IMIB), 30120 Murcia, Spain.
Manuel HidalgoRosenberg Clinical Cancer Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Hossein KhiabanianDepartment of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
Raul RabadánDepartment of Systems Biology, Columbia University Medical Center, New York, NY 10032, USA.
Fátima Al-ShahrourBioinformatics Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain.
Carmen GuerraMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain. Electronic address: mcguerra@cnio.es.
Mariano BarbacidMolecular Oncology Program, Centro Nacional de Investigaciones Oncológicas (CNIO), 28029 Madrid, Spain; Instituto Ramón y Cajal de Investigación Sanitaria (IRYCIS), 28034 Madrid, Spain. Electronic address: mbarbacid@cnio.es.
Spanish National Cancer Research Centre · ESInstituto Ramón y Cajal de Investigación Sanitaria · ESColumbia University Irving Medical Center · USAix-Marseille Université · FRBeth Israel Deaconess Medical Center · USCentre de Recherche en Cancérologie de Marseille · FRInstituto Murciano de Investigación Biosanitaria · ES
Funding
Systematic pharmacological targeting of the core mechanisms responsible for maintaining cancer cell stateU54CA209997 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI CALIFANO, ANDREA, HONIG, BARRY H · 2016 to 2021
$10.9MTopology of Cancer Evolution and HeterogeneityU54CA193313 · NCI · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI IAVARONE, ANTONIO, RABADAN, RAUL · 2015 to 2020
$10.4MNCI NIH HHS U54 CA193313NCI NIH HHS U54 CA209997
Abstract
Five-year survival for pancreatic ductal adenocarcinoma (PDAC) patients remains below 7% due to the lack of effective treatments. Here, we report that combined ablation of EGFR and c-RAF expression results in complete regression of a significant percentage of PDAC tumors driven by Kras/Trp53 mutations in genetically engineered mice. Moreover, systemic elimination of these targets induces toxicities that are well tolerated. Response to this targeted therapy correlates with transcriptional profiles that resemble those observed in human PDACs. Finally, inhibition of EGFR and c-RAF expression effectively blocked tumor progression in nine independent patient-derived xenografts carrying KRAS and TP53 mutations. These results open the door to the development of targeted therapies for PDAC patients.
Indexed as
AnimalsApoptosisCarcinoma, Pancreatic DuctalCell Line, TumorCell ProliferationErbB ReceptorsErlotinib HydrochlorideGefitinibGene Expression Regulation, NeoplasticHumansMice, 129 StrainMice, Inbred C57BLMice, TransgenicMutationPancreatic NeoplasmsProtein Kinase InhibitorsEGFR protein, humanEGFR protein, mouseErbB ReceptorsErlotinib HydrochlorideGefitinibHras protein, mouseKRAS protein, humanProtein Kinase InhibitorsProto-Oncogene Proteins c-rafProto-Oncogene Proteins p21(ras)Raf1 protein, humanRaf1 protein, mouseTP53 protein, humanTrp53 protein, mouseTumor Suppressor Protein p53Cdk4c-RafEGFRErlotinibPancreatic cancerPDX tumor modelstherapeutic mouse modelstranscriptional profilestumor regression
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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.