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Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

by Porzio, Rosa , Romano, Ida , Marchetti, Giovanni , Pinto, Carmine , Pedrazzi, Giuseppe , Crafa, Pellegrino , Bacchini, Gian P , Lagrasta, Costanza , Fanello, Silvia , Gardini, Giorgio , Negri, Francesca V , Bozzetti, Cecilia , Tomasello, Gianluca , Ardizzoni, Andrea , Sala, Roberto , Azzoni, Cinzia , Bottarelli, Lorena , Bisagni, Alessandra , Graiani, Gallia , Paties, Carlo , Tamagnini, Ione

in Adaptor Proteins, Signal Transducing / Adult / Aged / Aged, 80 and over / Angiogenesis / Antineoplastic Combined Chemotherapy Protocols / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / bevacizumab / Bevacizumab - administration & dosage / bevacizumab; colorectal cancer; DLL4; Notch activation; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Biomarkers; Case-Control Studies; Colorectal Neoplasms; Female; Humans; Intercellular Signaling Peptides and Proteins; Male; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Receptors, Notch; Retreatment; Treatment Outcome; Oncology; Cancer Research / Biomarkers / Calcium-Binding Proteins / Cancer therapies / Case-Control Studies / Chemotherapy / Clinical trials / Colorectal cancer / Colorectal Neoplasms / Colorectal Neoplasms - drug therapy / Colorectal Neoplasms - metabolism / Colorectal Neoplasms - mortality / Colorectal Neoplasms - pathology / DLL4 / Female / Humans / Hypoxia / Immunotherapy / Intercellular Signaling Peptides and Proteins / Intercellular Signaling Peptides and Proteins - metabolism / Ligands / Male / Metastasis / Middle Aged / Monoclonal antibodies / Neoplasm Metastasis / Neoplasm Staging / Notch activation / Receptors, Notch / Receptors, Notch - metabolism / Retreatment / Targeted cancer therapy / Treatment Outcome / Tumors

2015

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Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

2015

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2015

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Journal Article

Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

Porzio, Rosa,

Romano, Ida,

Marchetti, Giovanni,

Pinto, Carmine,

Pedrazzi, Giuseppe,

Crafa, Pellegrino,

Bacchini, Gian P,

Lagrasta, Costanza,

Fanello, Silvia,

Gardini, Giorgio,

Negri, Francesca V,

Bozzetti, Cecilia,

Tomasello, Gianluca,

Ardizzoni, Andrea,

Sala, Roberto,

Azzoni, Cinzia,

Bottarelli, Lorena,

Bisagni, Alessandra,

Graiani, Gallia,

Paties, Carlo,

Tamagnini, Ione

2015

Overview

To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). 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. 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. A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.

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Publisher

Future Medicine Ltd,Informa UK Limited

Subject

Adaptor Proteins, Signal Transducing

/ Adult

/ Aged

/ Aged, 80 and over

/ Angiogenesis

/ Antineoplastic Combined Chemotherapy Protocols

/ Antineoplastic Combined Chemotherapy Protocols - therapeutic use