title: Selective antitumor activity of ibrutinib in EGFR-mutant non-small cell lung cancer cells.
abstract: Ibrutinib, which irreversibly inhibits Bruton tyrosine kinase, was evaluated for antitumor activity in a panel of non-small cell lung cancer (NSCLC) cell lines and found to selectively inhibit growth of NSCLC cells carrying mutations in the epidermal growth factor receptor (EGFR) gene, including T790M mutant and erlotinib-resistant H1975 cells. Ibrutinib induced dose-dependent inhibition of phosphor-EGFR at both Y1068 and Y1173 sites, suggesting ibrutinib functions as an EGFR inhibitor. Survival was analyzed by Kaplan-Meier estimation and log-rank test. All statistical tests were two-sided. In vivo study showed that ibrutinib statistically significantly suppressed H1975 tumor growth and prolonged survival of the tumor bearing mice (n = 5 per group). The mean survival times for solvent- and erlotinib-treated mice were both 17.8 days (95% confidence interval [CI] = 14.3 to 21.3 days), while the mean survival time for ibrutinib-treated mice was 29.8 days (95% CI = 26.0 to 33.6 days, P = .008). Our results indicate that ibrutinib could be a candidate drug for treatment of EGFR-mutant NSCLC, including erlotinib-resistant tumors.
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Wen
authors.initials: W
authors.lastname: Gao
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Michael
authors.initials: M
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Haibo
authors.initials: H
authors.lastname: Lu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Shuhong
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Bingbing
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Zhishuo
authors.initials: Z
authors.lastname: Ou
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Liang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Gold
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: John
authors.initials: J
authors.lastname: Minna
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Jack A
authors.initials: JA
authors.lastname: Roth
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Wayne L
authors.initials: WL
authors.lastname: Hofstetter
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG).
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Swisher
authors.affiliation: Department of Thoracic and Cardiovascular Surgery (WG, LW, HL, SW, BD, JAR, WLH, SGS, BF) and Department of Lymphoma and Myeloma (MW, ZO, LZ) and Department of Thoracic/Head and Neck Medical Oncology (JVH, KAD), The University of Texas MD Anderson Cancer Center, Houston, TX; Hamon Center for Therapeutic Oncology, The Harold C. Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, TX (JM); Department of Oncology, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China (WG). bfang@mdanderson.org.
authors.forename: Bingliang
authors.initials: B
authors.lastname: Fang
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000235:genetics; D008715:Methionine; D051379:Mice; D009154:Mutation; D010880:Piperidines; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology; D013912:Threonine
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D011720:Pyrazoles; D011743:Pyrimidines; D011799:Quinazolines; C551803:ibrutinib; D013912:Threonine; D008715:Methionine; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D000225:Adenine