Journal
CLINICAL CANCER RESEARCH
Volume 19, Issue 5, Pages 1139-1146Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1078-0432.CCR-12-2127
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Funding
- NIH [CA130938, CA62924, CA122581]
- Sol Goldman Pancreatic Cancer Research Center
- Stewart Trust Fund
- Lustgarten Foundation
- Mary Lou Wootton Pancreatic Cancer Research Fund
- Michael Rolfe Pancreatic Cancer Foundation
- HERA Foundation
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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. Clin Cancer Res; 19(5); 1139-46. (C) 2012 AACR.
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