Cancer stem cells marker CD44 and Notch activation predict unfavorable prognosis in metastatic colon cancer patients treated with anti VEGF-therapy

Date 29 June 2016
Event ESMO World Congress on Gastrointestinal Cancer 2016
Session ESMO World Congress on Gastrointestinal Cancer 2016 - Abstracts book
Presenter F.V. Negri
Citation Annals of Oncology (2016) 27 (2): 1-85. 10.1093/annonc/mdw199
Authors F.V. Negri1, C. Bozzetti1, C. Azzoni2, L. Bottarelli2, A. Squadrilli2, G. Pedrazzi3, C. Lagrasta4, I. Tamagnini5, A. Bisagni6, R. Porzio1, G. Tomasello7, F. Leonardi2, C. Pinto6, A. Ardizzoni1, R. Sala8, F. Quaini2
  • 1Medical Oncology Unit, University Hospital of Parma, Parma, Italy, /
  • 2University Hospital of Parma, Parma, Italy, /
  • 3Health Physics Division, University of Parma, Parma, Italy, /
  • 4Department of Pathology, University Hospital of Parma, Parma, Italy, /
  • 5Arcispedale S. Maria Nuova, Reggio Emilia, Italy, /
  • 6Arcispedale Santa Maria Nuova, Reggio Emilia, Italy, /
  • 7Medical Oncology Division, Istituti Ospitalieri di Cremona, Cremona, Italy, /
  • 8University of Parma, Parma, Italy, /

Abstract

Notch pathway has been suggested to play an important role in regulating cancer stem cells (CSCs) in colon cancer. CSCs are responsible for cancer initiation, progression and may be involved in resistance to conventional therapies. Moreover, CSCs promote angiogenesis throughout several factors such as MDK, EGF, and IL-8. CD44 and CD133 are transmembrane glycoproteins reported as putative markers for isolating CSCs. Preclinical studies and a clinical study from our group (Negri et al, 2015) showed that strong Notch intracellular cleaved domain (NICD) is associated with resistance to anti-vascular endothelial growth factor (VEGF) therapy in colon cancer. Based on these reports, we evaluated NICD, CD44 and CD133 expression in a series of consecutive metastatic colon cancer patients treated with anti-VEGF monoclonal antibody bevacizumab within first-line clinical trials.