Serial assessment of human tumor burdens in mice by the analysis of circulating DNA.
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.
Rago
Carlo
C
The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Baltimore, Maryland, USA.
Huso
David L
DL
Diehl
Frank
F
Karim
Baktiar
B
Liu
Guosheng
G
Papadopoulos
Nickolas
N
Samuels
Yardena
Y
Velculescu
Victor E
VE
Vogelstein
Bert
B
Kinzler
Kenneth W
KW
Diaz
Luis A
LA
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood* / Q000235:genetics; D003110:Colonic Neoplasms / Q000097:blood* / Q000235:genetics / Q000473:pathology; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000097:blood*; D004195:Disease Models, Animal; D005260:Female; D045325:HCT116 Cells; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm