Strong Notch activation hinders bevacizumab efficacy in advanced colorectal cancer

Future Oncol. 2015;11(23):3167-74. doi: 10.2217/fon.15.218. Epub 2015 Nov 9.

Abstract

Aim: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC).

Materials & 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.

Conclusion: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.

Keywords: DLL4; Notch activation; bevacizumab; colorectal cancer.

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab / administration & dosage
  • Biomarkers
  • Calcium-Binding Proteins
  • Case-Control Studies
  • Colorectal Neoplasms / drug therapy*
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / mortality
  • Colorectal Neoplasms / pathology
  • Female
  • Humans
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasm Staging
  • Receptors, Notch / metabolism*
  • Retreatment
  • Treatment Outcome

Substances

  • Adaptor Proteins, Signal Transducing
  • Biomarkers
  • Calcium-Binding Proteins
  • DLL4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Receptors, Notch
  • Bevacizumab