TY - JOUR
T1 - Serial assessment of human tumor burdens in mice by the analysis of circulating DNA
AU - Rago, Carlo
AU - Huso, David L
AU - Diehl, Frank
AU - Karim, Baktiar
AU - Liu, Guosheng
AU - Papadopoulos, Nickolas
AU - Samuels, Yardena
AU - Velculescu, Victor E.
AU - Vogelstein, Bert
AU - Kinzler, Kenneth W.
AU - Diaz, Luis A.
PY - 2007/10/1
Y1 - 2007/10/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=35148841977&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=35148841977&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-0605
DO - 10.1158/0008-5472.CAN-07-0605
M3 - Article
C2 - 17909045
AN - SCOPUS:35148841977
SN - 0008-5472
VL - 67
SP - 9364
EP - 9370
JO - Cancer Research
JF - Cancer Research
IS - 19
ER -