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Cancer Research 67, 9364, October 1, 2007. doi: 10.1158/0008-5472.CAN-07-0605
© 2007 American Association for Cancer Research

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Experimental Therapeutics, Molecular Targets, and Chemical Biology

Serial Assessment of Human Tumor Burdens in Mice by the Analysis of Circulating DNA

Carlo Rago1,2, David L. Huso2,3, Frank Diehl1,2, Baktiar Karim3, Guosheng Liu3, Nickolas Papadopoulos1,2, Yardena Samuels1, Victor E. Velculescu1, Bert Vogelstein1,2, Kenneth W. Kinzler1,2 and Luis A. Diaz, Jr.1,2

1 The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, 2 The Sidney Kimmel Comprehensive Cancer Center, and 3 Department of Molecular and Comparative Pathobiology, The Johns Hopkins Medical Institutions, Baltimore, Maryland

Requests for reprints: Luis A. Diaz, Johns Hopkins Kimmel Comprehensive Cancer Center, 1650 Orleans Street, Cancer Research Building I, Room 590, Baltimore, MD 21231. Phone: 410-955-8878; Fax: 410-955-0548; E-mail: ldiaz1{at}jhmi.edu.

Internal human xenografts provide valuable animal models to study the microenvironments and metastatic processes occurring in human cancers. However, the use of such models is hampered by the logistical difficulties of reproducibly and simply assessing tumor burden. We developed a high-sensitivity assay for quantifying human DNA in small volumes of mouse plasma, enabling in-life monitoring of systemic tumor burden. Growth kinetics analyses of various xenograft models showed the utility of circulating human DNA as a biomarker. We found that human DNA concentration reproducibly increased with disease progression and decreased after successful therapeutic intervention. A marked, transient spike in circulating human tumor DNA occurred immediately after cytotoxic therapy or surgery. This simple assay may find broad utility in target validation studies and preclinical drug development programs. [Cancer Res 2007;67(19):9364–70]




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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
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Copyright © 2007 by the American Association for Cancer Research.