Off-target lapatinib activity sensitizes colon cancer cells through TRAIL death receptor up-regulation

Science Translational Medicine

Volumn 3, Issue 86, 2011, Pages

  Dolloff, Nathan G ^a,b   Mayes, Patrick A ^a   Hart, Lori S ^a   Dicker, David T ^a,b   Humphreys, Robin ^c   El Deiry, Wafik S ^a,b,d  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b PENN STATE COLLEGE OF MEDICINE   (United States)

^c GLAXOSMITHKLINE   (United States)

^d AMERICAN CANCER SOCIETY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CASPASE 8; CISPLATIN; DEATH RECEPTOR 4; DEATH RECEPTOR 5; DOXORUBICIN; EPIDERMAL GROWTH FACTOR RECEPTOR; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ETOPOSIDE; FLUOROURACIL; GEMCITABINE; IRINOTECAN; LAPATINIB; LEXATUMUMAB; MAPATUMUMAB; PROTEIN C JUN; STRESS ACTIVATED PROTEIN KINASE; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND; TUMOR NECROSIS FACTOR RELATED APOPTOSIS INDUCING LIGAND RECEPTOR; ANTINEOPLASTIC AGENT; QUINAZOLINE DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CANCER CELL CULTURE; CANCER INHIBITION; CELLULAR DISTRIBUTION; COLORECTAL CANCER; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG POTENTIATION; DRUG RECEPTOR BINDING; DRUG SENSITIVITY; DRUG SENSITIZATION; DRUG TARGETING; ENZYME ACTIVATION; HUMAN; HUMAN CELL; IMMUNOHISTOCHEMISTRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN CLEAVAGE; PROTEIN DETERMINATION; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; SIGNAL TRANSDUCTION; UPREGULATION; ANIMAL; APOPTOSIS; CELL STRAIN HCT116; CELL STRAIN HT29; CELL SURVIVAL; COLON TUMOR; DRUG EFFECT; DRUG SCREENING; FLUORESCENCE MICROSCOPY; METABOLISM; MOUSE; NUDE MOUSE; POLYACRYLAMIDE GEL ELECTROPHORESIS; TUMOR CELL LINE; WESTERN BLOTTING;

ANIMALS; ANTINEOPLASTIC AGENTS; APOPTOSIS; BLOTTING, WESTERN; CELL LINE, TUMOR; CELL SURVIVAL; COLONIC NEOPLASMS; ELECTROPHORESIS, POLYACRYLAMIDE GEL; HCT116 CELLS; HT29 CELLS; HUMANS; IMMUNOHISTOCHEMISTRY; MICE; MICE, NUDE; MICROSCOPY, FLUORESCENCE; QUINAZOLINES; RECEPTORS, TNF-RELATED APOPTOSIS-INDUCING LIGAND; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 79958186707     PISSN: 19466234     EISSN: 19466242     Source Type: Journal    
DOI: 10.1126/scitranslmed.3001384     Document Type: Article

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50. Acknowledgments: We thank the G.I. morphology core of University of Pennsylvania School of Medicine (P30 DK50306) for technical assistance with our histological analyses. We thank T. M. Gilmer of GlaxoSmithKline for providing lapatinib. Funding: W.S.E.-D. is an American Cancer Society Research Professor. The work was funded in part by support from NIH grants CA123258, CA105008, and CA135273, as well as from Penn State Hershey Cancer Institute laboratory start-up funds to W.S.E.-D. Author contributions: N.G.D. designed and performed all experiments, analyzed all the data, and wrote the paper; P.A.M. designed and performed the experiments; L.S.H. designed and performed the experiments; D.T.D. collected and analyzed all flow cytometry data; R.H. analyzed the data from experiments involving the TRAIL-R agonistic antibodies mapatumumab and lexatumumab; W.S.E.-D. designed all experiments, analyzed all the data, and revised the paper. Competing interests: The authors declare that they have no competing interests. Data and materials availability: We received lapatinib through a materials transfer agreement (MTA) with GlaxoSmithKline and lexatumumab and mapatumumab through an MTA with Human Genome Sciences Inc.