Rago Carlo, Huso David L, Diehl Frank, Karim Baktiar, Liu Guosheng, Papadopoulos Nickolas, Samuels Yardena, Velculescu Victor E, Vogelstein Bert, Kinzler Kenneth W, Diaz Luis A
The Ludwig Center for Cancer Genetics and Therapeutics and The Howard Hughes Medical Institute, Baltimore, Maryland, USA.
Cancer Res. 2007 Oct 1;67(19):9364-70. doi: 10.1158/0008-5472.CAN-07-0605.
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.
人源异种移植为研究人类癌症中发生的微环境和转移过程提供了有价值的动物模型。然而，此类模型的使用受到可重复性和简单评估肿瘤负荷的后勤困难的阻碍。我们开发了一种高灵敏度检测方法，用于定量检测少量小鼠血浆中的人类DNA，从而能够在活体中监测全身肿瘤负荷。对各种异种移植模型的生长动力学分析表明，循环人类DNA作为生物标志物具有实用性。我们发现，人类DNA浓度随着疾病进展而可重复性增加，并在成功的治疗干预后降低。细胞毒性治疗或手术后，循环人类肿瘤DNA会立即出现明显的、短暂的峰值。这种简单的检测方法可能在靶点验证研究和临床前药物开发项目中具有广泛的应用。
