title: Individual patient oesophageal cancer 3D models for tailored treatment.
abstract: BACKGROUND
  A model to predict chemotherapy response would provide a marked clinical benefit, enabling tailored treatment of oesophageal cancer, where less than half of patients respond to the routinely administered chemotherapy.
  
  
  METHODS
  Cancer cells were established from tumour biopsies taken from individual patients about to undergo neoadjuvant chemotherapy. A 3D-tumour growth assay (3D-TGA) was developed, in which cancer cells were grown with or without supporting mesenchymal cells, then subjected to chemo-sensitivity testing using the standard chemotherapy administered in clinic, and a novel emerging HDAC inhibitor, Panobinostat.
  
  
  RESULTS
  Individual patient's cancer cells could be expanded and screened within a clinically applicable timescale of 3 weeks. Incorporating mesenchymal support within the 3D-TGA significantly enhanced both the growth and drug resistance profiles of the patient's cancer cells. The ex vivo drug response in the presence, but not absence, of mesenchymal cells accurately reflected clinical chemo-sensitivity, as measured by tumour regression grade. Combination with Panobinostat enhanced response and proved efficacious in otherwise chemo-resistant tumours.
  
  
  CONCLUSIONS
  This novel method of establishing individual patient oesophageal cancers in the laboratory, from small endoscopic biopsies, enables clinically-relevant chemo-sensitivity testing, and reduces use of animals by providing more refined in vitro models for pre-screening of drugs. The 3D-TGA accurately predicted chemo-sensitivity in patients, and could be developed to guide tailored patient treatment. The incorporation of mesenchymal cells as the stromal cell component of the tumour micro-environment had a significant effect upon enhancing chemotherapy drug resistance in oesophageal cancer, and could prove a useful target for future drug development.
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.|Department of Upper GI Surgery, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: John H
authors.initials: JH
authors.lastname: Saunders
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: David
authors.initials: D
authors.lastname: Onion
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Pamela
authors.initials: P
authors.lastname: Collier
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: Dorrington
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Richard H
authors.initials: RH
authors.lastname: Argent
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Philip A
authors.initials: PA
authors.lastname: Clarke
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.|Department of Upper GI Surgery, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Alex M
authors.initials: AM
authors.lastname: Reece-Smith
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.|Department of Upper GI Surgery, City Hospital Campus, Nottingham University Hospitals NHS Trust, Nottingham, UK.
authors.forename: Simon L
authors.initials: SL
authors.lastname: Parsons
authors.affiliation: Cancer Biology Unit, Division of Cancer & Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Grabowska
mesh_terms: D000368:Aged; D015415:Biomarkers; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003131:Combined Modality Therapy; D019008:Drug Resistance, Neoplasm; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D010641:Phenotype; D057285:Precision Medicine / Q000379:methods; D016896:Treatment Outcome; D047368:Tumor Burden
chemical_list: D015415:Biomarkers
keywords: 3D models; chemotherapy; oesophageal cancer; personalised treatment; tumour microenvironment