Serial Assessment of Human Tumor Burdens in Mice by the Analysis of Circulating DNA
Abstract (Set) It is generally agreed that internal human xenografts provide the best 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. JHU researchers have developed a high-sensitivity PCR based assay for quantifying human DNA in small volumes of mouse plasma, enabling in-life monitoring of systemic tumor burden. Growth kinetic analyses of various xenograft models demonstrated the applicability of using circulating human DNA as a biomarker. 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 PCR based assay may find broad utility in target validation studies and preclinical drug development programs. Description (Set) Proposed Use (Set) This invention will allow scientists to quickly quantify the efficacy of candidate drugs in various pre-clinical animal model systems. This method is more expedient and cost effective than pathologic evaluation, but can be used to complement pathology or histology evaluations.
Diaz, Luis ,Kinzler, Kenneth,Rago, Carlo,Vogelstein, Bert
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