Serial assessment of human tumor burdens in mice by the analysis of circulating DNA

Carlo Rago, David L. Huso, Frank Diehl, Baktiar Karim, Guosheng Liu, Nickolas Papadopoulos, Yardena Samuels, Victor E. Velculescu, Bert Vogelstein, Kenneth W. Kinzler, Luis A. Diaz

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)9364-9370
Number of pages7
JournalCancer Research
Volume67
Issue number19
DOIs
StatePublished - Oct 1 2007

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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