title: A personalized preclinical model to evaluate the metastatic potential of patient-derived colon cancer initiating cells.
abstract: OBJECTIVE
  Within the aim of advancing precision oncology, we have generated a collection of patient-derived xenografts (PDX) characterized at the molecular level, and a preclinical model of colon cancer metastasis to evaluate drug-response and tumor progression.
  
  
  METHODS
  We derived cells from 32 primary colorectal carcinomas and eight liver metastases and generated PDX annotated for their clinical data, gene expression, mutational, and histopathological traits. Six models were injected orthotopically into the cecum wall of NOD-SCID mice in order to evaluate metastasis. Three of them were treated with chemotherapy (oxaliplatin) and three with API2 to target AKT activity. Tumor growth and metastasis progression were analyzed by positron emission tomography (PET).
  
  
  RESULTS
  Patient-derived cells generated tumor xenografts that recapitulated the same histopathological and genetic features as the original patients' carcinomas. We show an 87.5% tumor take rate that is one of the highest described for implanted cells derived from colorectal cancer patients. Cecal injection generated primary carcinomas and distant metastases. Oxaliplatin treatment prevented metastasis and API2 reduced tumor growth as evaluated by PET.
  
  
  CONCLUSIONS
  Our improved protocol for cancer cell engraftment has allowed us to build a rapidly expanding collection of colorectal PDX, annotated for their clinical data, gene expression, mutational, and histopathological statuses. We have also established a mouse model for metastatic colon cancer with patient-derived cells in order to monitor tumor growth, metastasis evolution, and response to treatment by PET. Our PDX models could become the best preclinical approach through which to validate new biomarkers or investigate the metastatic potential and drug-response of individual patients.
authors.affiliation: Authors' Affiliations: Translational Program, Stem Cells and Cancer Laboratory; Molecular Oncology Group; Genomics Cancer Group; and Translational Genomics Group, Vall d'Hebron Institute of Oncology (VHIO); Parc de Recerca Biomèdica de Barcelona (PRBB), Centre d'Imatge Molecular (CRC) Corporació Sanitària; Departments of Pathology, Medical Oncology, and HBP Surgery and Transplantation, Vall d'Hebron University Hospital, Universidad Autónoma de Barcelona; and General Surgery Service, Vall d'Hebron University Hospital, Barcelona, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Puig
authors.forename: Irene
authors.initials: I
authors.lastname: Chicote
authors.forename: Stephan P
authors.initials: SP
authors.lastname: Tenbaum
authors.forename: Oriol
authors.initials: O
authors.lastname: Arqués
authors.forename: José Raúl
authors.initials: JR
authors.lastname: Herance
authors.forename: Juan D
authors.initials: JD
authors.lastname: Gispert
authors.forename: José
authors.initials: J
authors.lastname: Jimenez
authors.forename: Stefania
authors.initials: S
authors.lastname: Landolfi
authors.forename: Karina
authors.initials: K
authors.lastname: Caci
authors.forename: Helena
authors.initials: H
authors.lastname: Allende
authors.forename: Leire
authors.initials: L
authors.lastname: Mendizabal
authors.forename: Debora
authors.initials: D
authors.lastname: Moreno
authors.forename: Ramón
authors.initials: R
authors.lastname: Charco
authors.forename: Eloy
authors.initials: E
authors.lastname: Espín
authors.forename: Aleix
authors.initials: A
authors.lastname: Prat
authors.forename: Maria Elena
authors.initials: ME
authors.lastname: Elez
authors.forename: Guillem
authors.initials: G
authors.lastname: Argilés
authors.forename: Ana
authors.initials: A
authors.lastname: Vivancos
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.forename: Santiago
authors.initials: S
authors.lastname: Rojas
authors.forename: Héctor G
authors.initials: HG
authors.lastname: Palmer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000556:secondary; D008297:Male; D051379:Mice; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D049268:Positron-Emission Tomography; D057285:Precision Medicine; D023041:Xenograft Model Antitumor Assays
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin