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Experimental Therapeutics, Molecular Targets, and Chemical Biology |
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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