Personalized Chemotherapy Profiling Using Cancer Cell Lines from Selectable Mice

• Type of Material: Article
• Authors: Hirohiko Kamiyama, Johns Hopkins University; Sherri Rauenzahn, Johns Hopkins University; Joong Sup Shim, Johns Hopkins University; Collins A. Karikari, Johns Hopkins University; Georg Feldmann, Johns Hopkins University; Li Hua, Johns Hopkins University; Mihoko Kamiyama, Johns Hopkins University; F. William Schuler, Johns Hopkins University; Ming-Tseh Lin, Johns Hopkins University; Robert M. Beaty, Johns Hopkins University; Balasubrmanyam Karanam, Johns Hopkins University; Hong Liang, Johns Hopkins University; Michael E. Mullendore, Johns Hopkins University; Guanglan Mo, Johns Hopkins University; Manuel Hidalgo, Johns Hopkins University; Elizabeth Jaffee, Johns Hopkins University; Ralph H. Hruban, Johns Hopkins University; Hyder Jinnah, Emory University; Richard B. S. Roden, Johns Hopkins University; Antonio Jimeno, Johns Hopkins University; Jun O. Liu, Johns Hopkins University; Anirban Maitra, Johns Hopkins University; James R. Eshleman, Johns Hopkins University
• Language: English
• Date: 2013-03-01
• Publisher: American Association for Cancer Research
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 American Association for Cancer Research.
• Final Published Version (URL): http://dx.doi.org/10.1158/1078-0432.CCR-12-2127
• Title of Journal or Parent Work: Clinical Cancer Research
• ISSN: 1078-0432
• Volume: 19
• Issue: 5
• Start Page: 1139
• End Page: 1146
• Grant/Funding Information: This work was funded in part from NIH grants CA130938 (JRE), CA62924 (Drs. Scott Kern, RHH, AM, JRE), CA122581 (RBSR), The Sol Goldman Pancreatic Cancer Research Center, The Stewart Trust Fund, The Lustgarten Foundation, the Mary Lou Wootton Pancreatic Cancer Research Fund, The Michael Rolfe Pancreatic Cancer Foundation and the HERA Foundation (RBSR).
• Keywords: INHIBITION; PANCREATIC-CANCER; Science & Technology; RESISTANCE ASSAYS; SENSITIVITY; OVARIAN-CANCER; ESTABLISHMENT; AGENTS; Oncology; BREAST; TRIPTOLIDE; TUMOR; Life Sciences & Biomedicine
• Research Categories: Health Sciences, Oncology

Abstract

Purpose: High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult because contaminating stromal cells overgrow the malignant cells. Experimental Design: We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts. Results: Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. Wescreened one cell line with a 3,131-drug panel and identified 77 U.S. Food and Drug Administration (FDA)-approved drugs with activity, and two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs. Conclusion: Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice.