title: Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer.
abstract: OBJECTIVE
  To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).
  
  
  METHODS
  Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone.
  
  
  RESULTS
  Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone.
  
  
  CONCLUSIONS
  A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.
authors.affiliation: Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Francesca V
authors.initials: FV
authors.lastname: Negri
authors.affiliation: Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Pellegrino
authors.initials: P
authors.lastname: Crafa
authors.affiliation: Department of Neuroscience, University of Parma, Via Volturno 39, 43126 Parma, Italy.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Pedrazzi
authors.affiliation: Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bozzetti
authors.affiliation: Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Costanza
authors.initials: C
authors.lastname: Lagrasta
authors.affiliation: Pathology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Gardini
authors.affiliation: Pathology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy.
authors.forename: Ione
authors.initials: I
authors.lastname: Tamagnini
authors.affiliation: Pathology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bisagni
authors.affiliation: Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Azzoni
authors.affiliation: Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Bottarelli
authors.affiliation: Department of Pathology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Gallia
authors.initials: G
authors.lastname: Graiani
authors.affiliation: Department of Radiology, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Ida
authors.initials: I
authors.lastname: Romano
authors.affiliation: Medical Oncology Unit, Azienda Unità Sanitaria Locale, Via Taverna 49, 29121 Piacenza, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Porzio
authors.affiliation: Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Gian P
authors.initials: GP
authors.lastname: Bacchini
authors.affiliation: Pathology Unit, Azienda Unità Sanitaria Locale, Via Taverna 49, 29121 Piacenza, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Paties
authors.affiliation: Medical Oncology Unit, Azienda Istituti Ospitalieri, Viale Concordia 1, 26100 Cremona, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Tomasello
authors.affiliation: Pathology Unit, Azienda Ospedaliera S.Maria Terni, Viale Tristano di Joannuccio 1, 05100 Terni, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Marchetti
authors.affiliation: Medical Oncology Unit, Istituto di Ricerca e Cura a Carattere Scientifico (IRCCS), Santa Maria Nuova Hospital, Viale Umberto I 50, 42123 Reggio Emilia, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Fanello
authors.affiliation: Medical Oncology Unit, University Hospital, Via Gramsci 14, 43126 Parma, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Pinto
authors.affiliation: Department of Biomedical Biotechnological & Translational Sciences (S.Bi.Bi.T), University of Parma, Via Volturno 39, 43126 Parma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Sala
authors.affiliation: Medical Oncology Unit, St Orsola-Malpighi Hospital, Via Albertoni 15, 40138 Bologna, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Ardizzoni
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab / Q000008:administration & dosage; D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D051880:Receptors, Notch / Q000378:metabolism*; D019233:Retreatment; D016896:Treatment Outcome
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015415:Biomarkers; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D051880:Receptors, Notch; D000068258:Bevacizumab
keywords: DLL4; Notch activation; bevacizumab; colorectal cancer