An in vivo platform for translational drug development in pancreatic cancer

被引:353
作者
Rubio-Viqueira, Belen
Jimeno, Antonio
Cusatis, George
Zhang, Xianfeng
Iacobuzio-Donahue, Christine
Karikari, Collins
Shi, Chanjusn
Danenberg, Kathleen
Danenberg, Peter V.
Kuramochi, Hidekazu
Tanaka, Koji
Singh, Sharat
Salimi-Moosavi, Hossein
Bouraoud, Nadia
Amador, Maria L.
Altiok, Soner
Kulesza, Piotr
Yeo, Charles
Messersmith, Wells
Eshleman, James
Hruban, Ralph H.
Maitra, Anirban
Hidalgo, Manuel
机构
[1] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Oncol, Baltimore, MD 21231 USA
[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Pathol, Baltimore, MD USA
[3] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Dept Surg, Baltimore, MD USA
[4] Johns Hopkins Univ, Sch Med, Sol Goldman Pancreat Canc Res Ctr, Baltimore, MD USA
[5] Response Genet Inc, Los Angeles, CA USA
[6] Monogram Biosci Inc, San Francisco, CA USA
[7] Univ So Calif, Dept Biochem & Mol Biol, Los Angeles, CA USA
关键词
D O I
10.1158/1078-0432.CCR-06-0113
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
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 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.
引用
收藏
页码:4652 / 4661
页数:10
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