title: Characterization of a large panel of patient-derived tumor xenografts representing the clinical heterogeneity of human colorectal cancer.
abstract: OBJECTIVE
  Patient-derived xenograft models are considered to represent the heterogeneity of human cancers and advanced preclinical models. Our consortium joins efforts to extensively develop and characterize a new collection of patient-derived colorectal cancer (CRC) models.
  
  
  METHODS
  From the 85 unsupervised surgical colorectal samples collection, 54 tumors were successfully xenografted in immunodeficient mice and rats, representing 35 primary tumors, 5 peritoneal carcinoses and 14 metastases. Histologic and molecular characterization of patient tumors, first and late passages on mice includes the sequence of key genes involved in CRC (i.e., APC, KRAS, TP53), aCGH, and transcriptomic analysis.
  
  
  RESULTS
  This comprehensive characterization shows that our collection recapitulates the clinical situation about the histopathology and molecular diversity of CRC. Moreover, patient tumors and corresponding models are clustering together allowing comparison studies between clinical and preclinical data. Hence, we conducted pharmacologic monotherapy studies with standard of care for CRC (5-fluorouracil, oxaliplatin, irinotecan, and cetuximab). Through this extensive in vivo analysis, we have shown the loss of human stroma cells after engraftment, observed a metastatic phenotype in some models, and finally compared the molecular profile with the drug sensitivity of each tumor model. Through an experimental cetuximab phase II trial, we confirmed the key role of KRAS mutation in cetuximab resistance.
  
  
  CONCLUSIONS
  This new collection could bring benefit to evaluate novel targeted therapeutic strategies and to better understand the basis for sensitivity or resistance of tumors from individual patients.
authors: Institut de Cancérologie Gustave Roussy, Villejuif, France.
authors: Sylvia
authors: S
authors: Julien
authors: Ana
authors: A
authors: Merino-Trigo
authors: Ludovic
authors: L
authors: Lacroix
authors: Marc
authors: M
authors: Pocard
authors: Diane
authors: D
authors: Goéré
authors: Pascale
authors: P
authors: Mariani
authors: Sophie
authors: S
authors: Landron
authors: Ludovic
authors: L
authors: Bigot
authors: Fariba
authors: F
authors: Nemati
authors: Peggy
authors: P
authors: Dartigues
authors: Louis-Bastien
authors: LB
authors: Weiswald
authors: Denis
authors: D
authors: Lantuas
authors: Loïc
authors: L
authors: Morgand
authors: Emmanuel
authors: E
authors: Pham
authors: Patrick
authors: P
authors: Gonin
authors: Virginie
authors: V
authors: Dangles-Marie
authors: Bastien
authors: B
authors: Job
authors: Philippe
authors: P
authors: Dessen
authors: Alain
authors: A
authors: Bruno
authors: Alain
authors: A
authors: Pierré
authors: Hugues
authors: H
authors: De Thé
authors: Hany
authors: H
authors: Soliman
authors: Manoel
authors: M
authors: Nunes
authors: Guillaume
authors: G
authors: Lardier
authors: Loreley
authors: L
authors: Calvet
authors: Brigitte
authors: B
authors: Demers
authors: Grégoire
authors: G
authors: Prévost
authors: Patricia
authors: P
authors: Vrignaud
authors: Sergio
authors: S
authors: Roman-Roman
authors: Olivier
authors: O
authors: Duchamp
authors: Cyril
authors: C
authors: Berthet
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D002471:Cell Transformation, Neoplastic / Q000187:drug effects*; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000077146:Irinotecan; D008297:Male; D051379:Mice; D053842:Microsatellite Instability; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D051381:Rats; D023041:Xenograft Model Antitumor Assays
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D000068818:Cetuximab; D005472:Fluorouracil; D002166:Camptothecin