Personalized chemotherapy profiling using cancer cell lines from selectable mice

Hirohiko Kamiyama, Sherri Rauenzahn, Joong Sup Shim, Collins A. Karikari, Georg Feldmann, Li Hua, Mihoko Kamiyama, F. William Schuler, Ming Tseh Lin, Robert M. Beaty, Balasubramanyam Karanam, Hong Liang, Michael E. Mullendore, Guanglan Mo, Manuel Hidalgo, Elizabeth Jaffee, Ralph H. Hruban, H. A. Jinnah, Richard B.S. Roden, Antonio JimenoJun O. Liu, Anirban Maitra, James R. Eshleman

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)1139-1146
Number of pages8
JournalClinical Cancer Research
Volume19
Issue number5
DOIs
StatePublished - Mar 1 2013

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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