David A. Barbie, MD

David A. Barbie, MD

Medical Oncology

Contact Information

Office Phone Number





877-332-4294 (new)
617-632-6190 (established)


David A. Barbie, MD

Dr. Barbie is the Director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute and an Associate Professor of Medicine at Harvard Medical School.  He is also Associate Director of the Belfer Center for Applied Cancer Science, as well as an Associate Member of the Broad Institute.  Dr. Barbie earned his undergraduate degree at Harvard College and M.D. degree at Harvard Medical School and was a Howard Hughes Medical Investigator Program Medical Student Research Fellow in Dr. Edward Harlow's laboratory at the MGH Cancer Center.  He then completed an MGH internal medicine residency and chief medical residency, a Dana-Farber Partners Oncology fellowship, and performed his post-doctoral work in Dr William Hahn's laboratory at Dana-Faber and the Broad Institute.  Currently, he is the principal investigator of his own laboratory at Dana-Farber while also seeing patients in the Lowe Center for Thoracic Oncology.



Director, Lowe Center for Thoracic Oncology
Associate Director, Belfer Center for Applied Cancer Research
Associate Professor of Medicine, Harvard Medical School


Clinical Interests

KRAS targeted therapy, Lung cancer, Translational oncology

Board Certification

  • Internal Medicine, 2005
  • Medical Oncology, 2008


  • Dana-Farber/Partners CancerCare, Medical Oncology


  • Massachusetts General Hospital, Chief Resident in Internal Medicine
  • Massachusetts General Hospital, Internal Medicine

Medical School

  • Harvard Medical School

Recent Awards

  • NIH R01 Award


  • V Foundation Scholar Award


  • ASCO Young Investigator Award 2009
  • NIH K08 Award 2010


    Translational Oncology/KRAS Targeted Therapy

    My interest as a medical oncologist and cancer biologist is to identify novel targets for cancer therapy. Specifically, I have focused on lung cancer clinically with a particular interest in targeting KRAS mutations, which have remained refractory to current therapies.

    We previously found that TBK1, a kinase that is normally involved in immune cell signaling, prevents apoptosis in cancer cells driven by oncogenic KRAS. Others have found that inhibition of the NF-kB and STAT pathways, in which TBK1 is involved, also results in impaired tumor growth in KRAS-driven mouse lung cancer. Recently, we discovered that a kinase inhibitor, momelotinib, inhibits TBK1 and JAK signaling and has activity in mouse models of Kras-driven lung cancer. Based on these findings, we have opened a trial together with Gilead Sciences combining momelotinib with the MEK inhibitor trametinib in treatment refractory KRAS mutant lung cancer.

    My overall goal is to continue this effort clinically and in the lab to refine combination therapy for KRAS-driven lung cancer and improve outcomes for this challenging disease.


      • Nonpathogenic E. coli engineered to surface display cytokines as a new platform for immunotherapy. Res Sq. 2024 Mar 22. View in: Pubmed

      • Affinity fine-tuning anti-CAIX CAR-T cells mitigate on-target off-tumor side effects. Mol Cancer. 2024 03 16; 23(1):56. View in: Pubmed

      • Lineage-specific canonical and non-canonical activity of EZH2 in advanced prostate cancer subtypes. Res Sq. 2024 Mar 04. View in: Pubmed

      • TREX1 inactivation unleashes cancer cell STING-interferon signaling and promotes anti-tumor immunity. Cancer Discov. 2024 Jan 10. View in: Pubmed

      • Single-cell functional genomics reveals determinants of sensitivity and resistance to natural killer cells in blood cancers. Immunity. 2023 Dec 12; 56(12):2816-2835.e13. View in: Pubmed

      • Unraveling the Intricacies of CD73/Adenosine Signaling: The Pulmonary Immune and Stromal Microenvironment in Lung Cancer. Cancers (Basel). 2023 Dec 04; 15(23). View in: Pubmed

      • Patient-Specific Vascularized Tumor Model: Blocking TAM Recruitment with Multispecific Antibodies Targeting CCR2 and CSF-1R. bioRxiv. 2023 Nov 29. View in: Pubmed

      • EDIL3 as an Angiogenic Target of Immune Exclusion Following Checkpoint Blockade. Cancer Immunol Res. 2023 11 01; 11(11):1493-1507. View in: Pubmed

      • Endocrine Therapy Synergizes with SMAC Mimetics to Potentiate Antigen Presentation and Tumor Regression in Hormone Receptor-Positive Breast Cancer. Cancer Res. 2023 10 02; 83(19):3284-3304. View in: Pubmed

      • Development of a Patient-Derived 3D Immuno-Oncology Platform to Potentiate Immunotherapy Responses in Ascites-Derived Circulating Tumor Cells. Cancers (Basel). 2023 Aug 16; 15(16). View in: Pubmed

      • Cotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer. J Clin Invest. 2023 08 15; 133(16). View in: Pubmed

      • ALK peptide vaccination restores the immunogenicity of ALK-rearranged non-small cell lung cancer. Nat Cancer. 2023 07; 4(7):1016-1035. View in: Pubmed

      • Molecular markers of metastatic disease in KRAS-mutant lung adenocarcinoma. Ann Oncol. 2023 07; 34(7):589-604. View in: Pubmed

      • Priming a vascular-selective cytokine response permits CD8+ T-cell entry into tumors. Nat Commun. 2023 04 14; 14(1):2122. View in: Pubmed

      • The germline factor DDX4 contributes to the chemoresistance of small cell lung cancer cells. Commun Biol. 2023 01 18; 6(1):65. View in: Pubmed

      • Targeting TBK1 to overcome resistance to cancer immunotherapy. Nature. 2023 03; 615(7950):158-167. View in: Pubmed

      • New Strategy for Promoting Vascularization in Tumor Spheroids in a Microfluidic Assay. Adv Healthc Mater. 2023 06; 12(14):e2201784. View in: Pubmed

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      • MET-Induced CD73 Restrains STING-Mediated Immunogenicity of EGFR-Mutant Lung Cancer. Cancer Res. 2022 11 02; 82(21):4079-4092. View in: Pubmed

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      • MPS1 inhibition primes immunogenicity of KRAS-LKB1 mutant lung cancer. Cancer Cell. 2022 10 10; 40(10):1128-1144.e8. View in: Pubmed

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      • Activation of Tumor-Cell STING Primes NK-Cell Therapy. Cancer Immunol Res. 2022 08 03; 10(8):947-961. View in: Pubmed

      • Dissecting the clinicopathologic, genomic, and immunophenotypic correlates of KRASG12D-mutated non-small-cell lung cancer. Ann Oncol. 2022 10; 33(10):1029-1040. View in: Pubmed

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      • Plasticity in the Absence of NOTCH Uncovers a RUNX2-Dependent Pathway in Small Cell Lung Cancer. Cancer Res. 2022 01 15; 82(2):248-263. View in: Pubmed

      • Diminished Efficacy of Programmed Death-(Ligand)1 Inhibition in STK11- and KEAP1-Mutant Lung Adenocarcinoma Is Affected by KRAS Mutation Status. J Thorac Oncol. 2022 03; 17(3):399-410. View in: Pubmed

      • Oncogenic switch and single-agent MET inhibitor sensitivity in a subset of EGFR-mutant lung cancer. Sci Transl Med. 2021 Sep; 13(609):eabb3738. View in: Pubmed

      • A robust vasculogenic microfluidic model using human immortalized endothelial cells and Thy1 positive fibroblasts. Biomaterials. 2021 09; 276:121032. View in: Pubmed

      • Reprogramming of the esophageal squamous carcinoma epigenome by SOX2 promotes ADAR1 dependence. Nat Genet. 2021 06; 53(6):881-894. View in: Pubmed

      • KRAS G12C inhibition and innate immune targeting. Expert Opin Ther Targets. 2021 03; 25(3):167-174. View in: Pubmed

      • EZH2 inhibition activates a dsRNA-STING-interferon stress axis that potentiates response to PD-1 checkpoint blockade in prostate cancer. Nat Cancer. 2021 04; 2(4):444-456. View in: Pubmed

      • Intrinsic Immunogenicity of Small Cell Lung Carcinoma Revealed by Its Cellular Plasticity. Cancer Discov. 2021 08; 11(8):1952-1969. View in: Pubmed

      • Dynamic single-cell RNA sequencing identifies immunotherapy persister cells following PD-1 blockade. J Clin Invest. 2021 01 19; 131(2). View in: Pubmed

      • Targeting the mutant p53 secretome. J Clin Invest. 2021 01 04; 131(1). View in: Pubmed

      • Engineering approaches for studying immune-tumor cell interactions and immunotherapy. iScience. 2021 Jan 22; 24(1):101985. View in: Pubmed

      • Turnaround Time of Plasma Next-Generation Sequencing in Thoracic Oncology Patients: A Quality Improvement Analysis. JCO Precis Oncol. 2020; 4. View in: Pubmed

      • Integration of multiomic annotation data to prioritize and characterize inflammation and immune-related risk variants in squamous cell lung cancer. Genet Epidemiol. 2021 02; 45(1):99-114. View in: Pubmed

      • Tumor-Derived cGAMP Regulates Activation of the Vasculature. Front Immunol. 2020; 11:2090. View in: Pubmed

      • Inactivation of Fbxw7 Impairs dsRNA Sensing and Confers Resistance to PD-1 Blockade. Cancer Discov. 2020 09; 10(9):1296-1311. View in: Pubmed

      • EGFR blockade activates interferon. Nat Cancer. 2020 04; 1(4):376-378. View in: Pubmed

      • TBK1 Activation by VHL Loss in Renal Cell Carcinoma: A Novel HIF-Independent Vulnerability. Cancer Discov. 2020 03; 10(3):348-350. View in: Pubmed

      • Use of ExVivo Patient-Derived Tumor Organotypic Spheroids to Identify Combination Therapies for HER2 Mutant Non-Small Cell Lung Cancer. Clin Cancer Res. 2020 05 15; 26(10):2393-2403. View in: Pubmed

      • Treatment-Induced Tumor Dormancy through YAP-Mediated Transcriptional Reprogramming of the Apoptotic Pathway. Cancer Cell. 2020 01 13; 37(1):104-122.e12. View in: Pubmed

      • Defining the landscape of ATP-competitive inhibitor resistance residues in protein kinases. Nat Struct Mol Biol. 2020 01; 27(1):92-104. View in: Pubmed

      • Clonal Selection Drives NF-?B Activation in Recurrent Nasopharyngeal Carcinoma. Cancer Res. 2019 12 01; 79(23):5915-5916. View in: Pubmed

      • Phosphorylation of RAB7 by TBK1/IKKe Regulates Innate Immune Signaling in Triple-Negative Breast Cancer. Cancer Res. 2020 01 01; 80(1):44-56. View in: Pubmed

      • Combination Olaparib and Temozolomide in Relapsed Small-Cell Lung Cancer. Cancer Discov. 2019 10; 9(10):1372-1387. View in: Pubmed

      • Retinoblastoma Inactivation Induces a Protumoral Microenvironment via Enhanced CCL2 Secretion. Cancer Res. 2019 08 01; 79(15):3903-3915. View in: Pubmed

      • Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. 2019 Jan 10; 176(1-2):404. View in: Pubmed

      • The kinases IKBKE and TBK1 regulate MYC-dependent survival pathways through YB-1 in AML and are targets for therapy. Blood Adv. 2018 12 11; 2(23):3428-3442. View in: Pubmed

      • A Cancer Cell Program Promotes T Cell Exclusion and Resistance to Checkpoint Blockade. Cell. 2018 11 01; 175(4):984-997.e24. View in: Pubmed

      • Defining T Cell States Associated with Response to Checkpoint Immunotherapy in Melanoma. Cell. 2018 11 01; 175(4):998-1013.e20. View in: Pubmed

      • Tumor cGAMP Awakens the Natural Killers. Immunity. 2018 10 16; 49(4):585-587. View in: Pubmed

      • 3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. Lab Chip. 2018 10 09; 18(20):3129-3143. View in: Pubmed

      • Suppression of STING Associated with LKB1 Loss in KRAS-Driven Lung Cancer. Cancer Discov. 2019 01; 9(1):34-45. View in: Pubmed

      • A High-Throughput Immune-Oncology Screen Identifies EGFR Inhibitors as Potent Enhancers of Antigen-Specific Cytotoxic T-lymphocyte Tumor Cell Killing. Cancer Immunol Res. 2018 12; 6(12):1511-1523. View in: Pubmed

      • Overcoming Resistance to Dual Innate Immune and MEK Inhibition Downstream of KRAS. Cancer Cell. 2018 09 10; 34(3):439-452.e6. View in: Pubmed

      • Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors. Nat Genet. 2018 09; 50(9):1271-1281. View in: Pubmed

      • Phase 1B Study of Momelotinib Combined With Trametinib in Metastatic, Kirsten Rat Sarcoma Viral Oncogene Homolog-Mutated Non-Small-Cell Lung Cancer After Platinum-Based Chemotherapy Treatment Failure. Clin Lung Cancer. 2018 11; 19(6):e853-e859. View in: Pubmed

      • Phase 1 dose-escalation study of momelotinib, a Janus kinase 1/2 inhibitor, combined with gemcitabine and nab-paclitaxel in patients with previously untreated metastatic pancreatic ductal adenocarcinoma. Invest New Drugs. 2019 02; 37(1):159-165. View in: Pubmed

      • Tumor innate immunity primed by specific interferon-stimulated endogenous retroviruses. Nat Med. 2018 08; 24(8):1143-1150. View in: Pubmed

      • Assessing Therapeutic Efficacy of MEK Inhibition in a KRASG12C-Driven Mouse Model of Lung Cancer. Clin Cancer Res. 2018 10 01; 24(19):4854-4864. View in: Pubmed

      • Plasma inflammatory cytokines and survival of pancreatic cancer patients. Clin Transl Gastroenterol. 2018 04 25; 9(4):145. View in: Pubmed

      • RASA1/NF1-Mutant Lung Cancer: Racing to the Clinic? Clin Cancer Res. 2018 03 15; 24(6):1243-1245. View in: Pubmed

      • Mechanisms of resistance to immune checkpoint inhibitors. Br J Cancer. 2018 01; 118(1):9-16. View in: Pubmed

      • ER Stress Signaling Promotes the Survival of Cancer "Persister Cells" Tolerant to EGFR Tyrosine Kinase Inhibitors. Cancer Res. 2018 02 15; 78(4):1044-1057. View in: Pubmed

      • Ex Vivo Profiling of PD-1 Blockade Using Organotypic Tumor Spheroids. Cancer Discov. 2018 02; 8(2):196-215. View in: Pubmed

      • CDK4/6 Inhibition Augments Antitumor Immunity by Enhancing T-cell Activation. Cancer Discov. 2018 02; 8(2):216-233. View in: Pubmed

      • Molecular and Genomic Determinants of Response to Immune Checkpoint Inhibition in Cancer. Annu Rev Med. 2018 01 29; 69:333-347. View in: Pubmed

      • Decomposing Oncogenic Transcriptional Signatures to Generate Maps of Divergent Cellular States. Cell Syst. 2017 08 23; 5(2):105-118.e9. View in: Pubmed

      • Refining Targeted Therapy Opportunities for BRAF-Mutant Melanoma. Cancer Discov. 2017 08; 7(8):799-801. View in: Pubmed

      • The RB-IL-6 axis controls self-renewal and endocrine therapy resistance by fine-tuning mitochondrial activity. Oncogene. 2017 09 07; 36(36):5145-5157. View in: Pubmed

      • Synergistic Immunostimulatory Effects and Therapeutic Benefit of Combined Histone Deacetylase and Bromodomain Inhibition in Non-Small Cell Lung Cancer. Cancer Discov. 2017 08; 7(8):852-867. View in: Pubmed

      • MicroRNA-140 mediates RB tumor suppressor function to control stem cell-like activity through interleukin-6. Oncotarget. 2017 Feb 21; 8(8):13872-13885. View in: Pubmed

      • Tumor SQSTM1 (p62) expression and T cells in colorectal cancer. Oncoimmunology. 2017; 6(3):e1284720. View in: Pubmed

      • Cytotoxic T Cells in PD-L1-Positive Malignant Pleural Mesotheliomas Are Counterbalanced by Distinct Immunosuppressive Factors. Cancer Immunol Res. 2016 12; 4(12):1038-1048. View in: Pubmed

      • Fine needle aspirate flow cytometric phenotyping characterizes immunosuppressive nature of the mesothelioma microenvironment. Sci Rep. 2016 08 19; 6:31745. View in: Pubmed

      • Inflammation as a driver and vulnerability of KRAS mediated oncogenesis. Semin Cell Dev Biol. 2016 10; 58:127-35. View in: Pubmed

      • Characterizing genomic alterations in cancer by complementary functional associations. Nat Biotechnol. 2016 05; 34(5):539-46. View in: Pubmed

      • Autophagy Inhibition Dysregulates TBK1 Signaling and Promotes Pancreatic Inflammation. Cancer Immunol Res. 2016 06; 4(6):520-30. View in: Pubmed

      • STK11/LKB1 Deficiency Promotes Neutrophil Recruitment and Proinflammatory Cytokine Production to Suppress T-cell Activity in the Lung Tumor Microenvironment. Cancer Res. 2016 Mar 01; 76(5):999-1008. View in: Pubmed

      • Doxycycline: new tricks for an old drug. Oncotarget. 2015 Aug 14; 6(23):19336-7. View in: Pubmed

      • Metabolic Rewiring by Oncogenic BRAF V600E Links Ketogenesis Pathway to BRAF-MEK1 Signaling. Mol Cell. 2015 Aug 06; 59(3):345-358. View in: Pubmed

      • Long-term Benefit of PD-L1 Blockade in Lung Cancer Associated with JAK3 Activation. Cancer Immunol Res. 2015 Aug; 3(8):855-63. View in: Pubmed

      • Response to Crizotinib in a Patient With Lung Adenocarcinoma Harboring a MET Splice Site Mutation. Clin Lung Cancer. 2015 Sep; 16(5):e101-4. View in: Pubmed

      • Targeting transcriptional addictions in small cell lung cancer with a covalent CDK7 inhibitor. Cancer Cell. 2014 Dec 08; 26(6):909-922. View in: Pubmed

      • Targeting an IKBKE cytokine network impairs triple-negative breast cancer growth. J Clin Invest. 2014 Dec; 124(12):5411-23. View in: Pubmed

      • Development of covalent inhibitors that can overcome resistance to first-generation FGFR kinase inhibitors. Proc Natl Acad Sci U S A. 2014 Nov 11; 111(45):E4869-77. View in: Pubmed

      • Targeting pathways downstream of KRAS in lung adenocarcinoma. Pharmacogenomics. 2014 Aug; 15(11):1507-18. View in: Pubmed

      • Targeting cytokine networks in KRAS-driven tumorigenesis. Expert Rev Anticancer Ther. 2014 Aug; 14(8):869-71. View in: Pubmed

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      • Whole-exome sequencing and clinical interpretation of formalin-fixed, paraffin-embedded tumor samples to guide precision cancer medicine. Nat Med. 2014 Jun; 20(6):682-8. View in: Pubmed

      • Requirement for CDK6 in MLL-rearranged acute myeloid leukemia. Blood. 2014 Jul 03; 124(1):13-23. View in: Pubmed

      • Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit. Cancer Discov. 2014 Apr; 4(4):452-65. View in: Pubmed

      • Systematic interrogation of 3q26 identifies TLOC1 and SKIL as cancer drivers. Cancer Discov. 2013 Sep; 3(9):1044-57. View in: Pubmed

      • Structure and ubiquitination-dependent activation of TANK-binding kinase 1. Cell Rep. 2013 Mar 28; 3(3):747-58. View in: Pubmed

      • Functional genomics and cancer drug target discovery. Curr Opin Mol Ther. 2010 Jun; 12(3):284-93. View in: Pubmed

      • Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1. Nature. 2009 Nov 05; 462(7269):108-12. View in: Pubmed

      • AKT-independent signaling downstream of oncogenic PIK3CA mutations in human cancer. Cancer Cell. 2009 Jul 07; 16(1):21-32. View in: Pubmed

      • Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell. 2009 May 29; 137(5):821-34. View in: Pubmed

      • Highly parallel identification of essential genes in cancer cells. Proc Natl Acad Sci U S A. 2008 Dec 23; 105(51):20380-5. View in: Pubmed

      • Destablization of the Cancer Genome. DeVita, Hellman & Rosenberg's Cancer: Principle and Practice of Oncology. 2008; 35-51. View in: Pubmed

      • Destablization of the Cancer Genome. DeVita, Hellman & Rosenberg's Cancer: Principle and Practice of Oncology. 2008; 35-51. View in: Pubmed

      • Pharmacology of Cancer: Genome Synthesis, Stability, and Maintenance. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2008; 675-699. View in: Pubmed

      • Pharmacology of Cancer: Signal Transduction. Principles of Pharmacology: The Pathophysiologic Basis of Drug Therapy. 2008; 701-717. View in: Pubmed

      • Hematology-Oncology. Pocket Medicine. 2008; 5.1-5.36. View in: Pubmed

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      • Hematology-Oncology. Pocket Medicine. 2008; 5.1-5.36. View in: Pubmed

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      • Eosinophilic gastroenteritis associated with systemic lupus erythematosus. J Clin Gastroenterol. 2004 Nov-Dec; 38(10):883-6. View in: Pubmed

      • A-type lamins regulate retinoblastoma protein function by promoting subnuclear localization and preventing proteasomal degradation. Proc Natl Acad Sci U S A. 2004 Jun 29; 101(26):9677-82. View in: Pubmed

      • Nuclear reorganization of mammalian DNA synthesis prior to cell cycle exit. Mol Cell Biol. 2004 Jan; 24(2):595-607. View in: Pubmed

      • Mullerian Inhibiting Substance inhibits cervical cancer cell growth via a pathway involving p130 and p107. Proc Natl Acad Sci U S A. 2003 Dec 23; 100(26):15601-6. View in: Pubmed

      • Nuclear Organization of Mammalian DNA Replication. 2002. View in: Pubmed

      • RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest. Mol Cell Biol. 2001 Apr; 21(8):2918-32. View in: Pubmed

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      • NPAT links cyclin E-Cdk2 to the regulation of replication-dependent histone gene transcription. Genes Dev. 2000 Sep 15; 14(18):2283-97. View in: Pubmed

      • Human fibroblast commitment to a senescence-like state in response to histone deacetylase inhibitors is cell cycle dependent. Mol Cell Biol. 1996 Sep; 16(9):5210-8. View in: Pubmed


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