title: Combining bevacizumab and chemoradiation in rectal cancer. Translational results of the AXEBeam trial.
abstract: BACKGROUND
  This study characterises molecular effect of bevacizumab, and explores the relation of molecular and genetic markers with response to bevacizumab combined with chemoradiotherapy (CRT).
  
  
  METHODS
  From a subset of 59 patients of 84 rectal cancer patients included in a phase II study combining bevacizumab with CRT, tumour and blood samples were collected before and during treatment, offering the possibility to evaluate changes induced by one dose of bevacizumab. We performed cDNA microarrays, stains for CD31/CD34 combined with α-SMA and CA-IX, as well as enzyme-linked immunosorbent assay (ELISA) for circulating angiogenic proteins. Markers were related with the pathological response of patients.
  
  
  RESULTS
  One dose of bevacizumab changed the expression of 14 genes and led to a significant decrease in microvessel density and in the proportion of pericyte-covered blood vessels, and a small but nonsignificant increase in hypoxia. Alterations in angiogenic processes after bevacizumab delivery were only detected in responding tumours. Lower PDGFA expression and PDGF-BB levels, less pericyte-covered blood vessels and higher CA-IX expression were found after bevacizumab treatment only in patients with pathological complete response.
  
  
  CONCLUSIONS
  We could not support the 'normalization hypothesis' and suggest a role for PDGFA, PDGF-BB, CA-IX and α-SMA. Validation in larger patient groups is needed.
authors: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium.
authors: M
authors: M
authors: Verstraete
authors: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium.
authors: A
authors: A
authors: Debucquoy
authors: Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: J
authors: J
authors: Dekervel
authors: Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: J
authors: J
authors: van Pelt
authors: Laboratory of Hepatology, Department of Clinical and Experimental Medicine, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: C
authors: C
authors: Verslype
authors: Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium.
authors: E
authors: E
authors: Devos
authors: Department of Digestive Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: G
authors: G
authors: Chiritescu
authors: Department of Digestive Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: K
authors: K
authors: Dumon
authors: Department of Abdominal Surgery, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: A
authors: A
authors: D'Hoore
authors: 1] Laboratory of Cancer Data Fusion, KU Leuven, Leuven, Belgium [2] Stanford Center for Biomedical Informatics Research, Stanford University, Stanford, CA, USA.
authors: O
authors: O
authors: Gevaert
authors: Department of Pathology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: X
authors: X
authors: Sagaert
authors: Department of Digestive Oncology, University Hospitals Leuven, KU Leuven, Leuven, Belgium.
authors: E
authors: E
authors: Van Cutsem
authors: 1] Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, Leuven, Belgium [2] Radiation Oncology, University Hospitals Leuven & Laboratory of Experimental Radiotherapy, Leuven, Belgium.
authors: K
authors: K
authors: Haustermans
mesh_terms: D000328:Adult; D000368:Aged; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000494:pharmacology; D000068258:Bevacizumab; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D059248:Chemoradiotherapy; D017322:Clinical Trials, Phase II as Topic; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D012004:Rectal Neoplasms / Q000097:blood / Q000473:pathology / Q000628:therapy*; D057170:Translational Research, Biomedical; D016896:Treatment Outcome
chemical_list: D020533:Angiogenesis Inhibitors; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D000068258:Bevacizumab