Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

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 chemo...

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Bibliographic Details
Published in:Future oncology (London, England) England), 2015-01, Vol.11 (23), p.3167-3174
Main Authors: Negri, Francesca V, Crafa, Pellegrino, Pedrazzi, Giuseppe, Bozzetti, Cecilia, Lagrasta, Costanza, Gardini, Giorgio, Tamagnini, Ione, Bisagni, Alessandra, Azzoni, Cinzia, Bottarelli, Lorena, Graiani, Gallia, Romano, Ida, Porzio, Rosa, Bacchini, Gian P, Paties, Carlo, Tomasello, Gianluca, Marchetti, Giovanni, Fanello, Silvia, Pinto, Carmine, Sala, Roberto, Ardizzoni, Andrea
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Angiogenesis
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
bevacizumab
Bevacizumab - administration & dosage
Biomarkers
Cancer therapies
Case-Control Studies
Chemotherapy
Clinical trials
Colorectal cancer
Colorectal Neoplasms - drug therapy
Colorectal Neoplasms - metabolism
Colorectal Neoplasms - mortality
Colorectal Neoplasms - pathology
DLL4
Female
Humans
Hypoxia
Immunotherapy
Intercellular Signaling Peptides and Proteins - metabolism
Ligands
Male
Metastasis
Middle Aged
Monoclonal antibodies
Neoplasm Metastasis
Neoplasm Staging
Notch activation
Receptors, Notch - metabolism
Retreatment
Targeted cancer therapy
Treatment Outcome
Tumors
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Summary: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.
ISSN:1479-6694
1744-8301
DOI:10.2217/fon.15.218