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: Belen Rubio-Viqueira, Antonio Jimeno, George Cusatis, Xianfeng Zhang, Christine Iacobuzio-Donahue, Collins Karikari, Chanjusn Shi, Kathleen Danenberg, Peter V Danenberg, Hidekazu Kuramochi, Koji Tanaka, Sharat Singh, Hossein Salimi-Moosavi, Nadia Bouraoud, Maria L Amador, Soner Altiok, Piotr Kulesza, Charles Yeo, Wells Messersmith, James Eshleman, Ralph H Hruban, Anirban Maitra, Manuel Hidalgo
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 12 Issue 15 Pg. 4652-61 (Aug 01 2006) ISSN: 1078-0432 [Print] United States
• PMID: 16899615 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2-(2-chloro-4-iodophenylamino)-N-cyclopropylmethoxy-3,4-difluorobenzamide
• Antineoplastic Agents
• Benzamides
• Deoxycytidine
• temsirolimus
• Sirolimus
• Gemcitabine

Topics

• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Benzamides (administration & dosage, pharmacokinetics)
• Carcinoma (drug therapy)
• Deoxycytidine (administration & dosage, analogs & derivatives, pharmacokinetics)
• Disease Models, Animal
• Female
• Humans
• Injections, Intraperitoneal
• Injections, Subcutaneous
• Kinetics
• Mice
• Mice, Nude
• Pancreatic Neoplasms (drug therapy, pathology)
• Predictive Value of Tests
• Sirolimus (administration & dosage, analogs & derivatives, pharmacokinetics)
• Transplantation, Heterologous
• Xenograft Model Antitumor Assays (methods)
• Gemcitabine