The Sol Goldman Pancreatic Cancer Research Center, Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA.
Clin Cancer Res. 2013 Mar 1;19(5):1139-46. doi: 10.1158/1078-0432.CCR-12-2127. Epub 2013 Jan 22.
High-throughput chemosensitivity testing of low-passage cancer cell lines can be used to prioritize agents for personalized chemotherapy. However, generating cell lines from primary cancers is difficult because contaminating stromal cells overgrow the malignant cells.
We produced a series of hypoxanthine phosphoribosyl transferase (hprt)-null immunodeficient mice. During growth of human cancers in these mice, hprt-null murine stromal cells replace their human counterparts.
Pancreatic and ovarian cancers explanted from these mice were grown in selection media to produce pure human cancer cell lines. We screened one cell line with a 3,131-drug panel and identified 77 U.S. Food and Drug Administration (FDA)-approved drugs with activity, and two novel drugs to which the cell line was uniquely sensitive. Xenografts of this carcinoma were selectively responsive to both drugs.
Chemotherapy can be personalized using patient-specific cell lines derived in biochemically selectable mice.
高通量化学敏感性测试低传代癌细胞系可用于优先考虑用于个体化化疗的药物。然而，从原发性癌症中产生细胞系是困难的，因为污染的基质细胞会使恶性细胞过度生长。
我们生产了一系列次黄嘌呤磷酸核糖转移酶（hprt）-缺陷免疫缺陷小鼠。在这些小鼠中生长人类癌症时，hprt-缺陷的鼠基质细胞取代了它们的人类对应物。
从这些小鼠中取出的胰腺和卵巢癌在选择培养基中生长，以产生纯人类癌细胞系。我们用 3131 种药物进行了筛选，发现有 77 种美国食品和药物管理局（FDA）批准的药物具有活性，还有两种新型药物对该细胞系具有独特的敏感性。该癌的异种移植物对这两种药物均有选择性反应。
可以使用在生化可选择的小鼠中衍生的患者特异性细胞系进行化疗个性化治疗。
