title: An in vivo platform for translational drug development in pancreatic cancer.
abstract: Effective development of targeted anticancer agents includes the definition of the optimal biological dose and biomarkers of drug activity. Currently available preclinical models are not optimal to this end. We aimed at generating a model for translational drug development using pancreatic cancer as a prototype. Resected pancreatic cancers from 14 patients were xenografted and expanded in successive groups of nude mice to develop cohorts of tumor-bearing mice suitable for drug therapy in simulated early clinical trials. The xenografted tumors maintain their fundamental genotypic features despite serial passages and recapitulate the genetic heterogeneity of pancreatic cancer. The in vivo platform is useful for integrating drug screening with biomarker discovery. Passages of tumors in successive cohorts of mice do not change their susceptibility to anticancer agents and represent a perpetual live bank, facilitating the application of new technologies that will result in the creation of an integrated stable database of tumor-drug response data and biomarkers.
authors.affiliation: Department of Oncology, Sidney Kimmel Comprehensive Cancer Center and the Sol Goldman Pancreatic Cancer Research Center at Johns Hopkins, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
authors.forename: Belen
authors.initials: B
authors.lastname: Rubio-Viqueira
authors.forename: Antonio
authors.initials: A
authors.lastname: Jimeno
authors.forename: George
authors.initials: G
authors.lastname: Cusatis
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Zhang
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.forename: Collins
authors.initials: C
authors.lastname: Karikari
authors.forename: Chanjusn
authors.initials: C
authors.lastname: Shi
authors.forename: Kathleen
authors.initials: K
authors.lastname: Danenberg
authors.forename: Peter V
authors.initials: PV
authors.lastname: Danenberg
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Kuramochi
authors.forename: Koji
authors.initials: K
authors.lastname: Tanaka
authors.forename: Sharat
authors.initials: S
authors.lastname: Singh
authors.forename: Hossein
authors.initials: H
authors.lastname: Salimi-Moosavi
authors.forename: Nadia
authors.initials: N
authors.lastname: Bouraoud
authors.forename: Maria L
authors.initials: ML
authors.lastname: Amador
authors.forename: Soner
authors.initials: S
authors.lastname: Altiok
authors.forename: Piotr
authors.initials: P
authors.lastname: Kulesza
authors.forename: Charles
authors.initials: C
authors.lastname: Yeo
authors.forename: Wells
authors.initials: W
authors.lastname: Messersmith
authors.forename: James
authors.initials: J
authors.lastname: Eshleman
authors.forename: Ralph H
authors.initials: RH
authors.lastname: Hruban
authors.forename: Anirban
authors.initials: A
authors.lastname: Maitra
authors.forename: Manuel
authors.initials: M
authors.lastname: Hidalgo
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001549:Benzamides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002277:Carcinoma / Q000188:drug therapy*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D007700:Kinetics; D051379:Mice; D008819:Mice, Nude; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D011237:Predictive Value of Tests; D020123:Sirolimus / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D014183:Transplantation, Heterologous; D023041:Xenograft Model Antitumor Assays / Q000379:methods*; D000093542:Gemcitabine
chemical_list: C120227:2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide; D000970:Antineoplastic Agents; D001549:Benzamides; D003841:Deoxycytidine; C401859:temsirolimus; D020123:Sirolimus; D000093542:Gemcitabine