Personalized chemotherapy profiling using cancer cell lines from selectable mice.

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. We screened 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.

• Authors: 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 Jimeno, Jun O Liu, Anirban Maitra, James R Eshleman
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 19 Issue 5 Pg. 1139-46 (Mar 01 2013) ISSN: 1557-3265 [Electronic] United States
• PMID: 23340293 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Antibiotics, Antineoplastic
• Cardiotonic Agents
• Interleukin Receptor Common gamma Subunit
• Digitoxin
• Hypoxanthine Phosphoribosyltransferase
• Nogalamycin

Topics

• Animals
• Antibiotics, Antineoplastic (pharmacology)
• Carcinoma, Pancreatic Ductal (drug therapy, metabolism, pathology)
• Cardiotonic Agents (pharmacology)
• Digitoxin (pharmacology)
• Female
• Humans
• Hypoxanthine Phosphoribosyltransferase (genetics)
• Interleukin Receptor Common gamma Subunit
• Male
• Mice
• Mice, Nude
• Mice, SCID
• Nogalamycin (pharmacology)
• Ovarian Neoplasms (drug therapy, metabolism, pathology)
• Pancreatic Neoplasms (drug therapy, metabolism, pathology)
• Precision Medicine
• Stromal Cells (drug effects, metabolism, pathology)
• Tumor Cells, Cultured