Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
Science. 2014 Jul 11;345(6193):216-20. doi: 10.1126/science.1253533.
Circulating tumor cells (CTCs) are present at low concentrations in the peripheral blood of patients with solid tumors. It has been proposed that the isolation, ex vivo culture, and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns of drug susceptibility in individual patients as their tumors acquire new mutations. In a proof-of-concept study, we established CTC cultures from six patients with estrogen receptor-positive breast cancer. Three of five CTC lines tested were tumorigenic in mice. Genome sequencing of the CTC lines revealed preexisting mutations in the PIK3CA gene and newly acquired mutations in the estrogen receptor gene (ESR1), PIK3CA gene, and fibroblast growth factor receptor gene (FGFR2), among others. Drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture conditions, this strategy may help identify the best therapies for individual cancer patients over the course of their disease.
循环肿瘤细胞 (CTCs) 在实体瘤患者的外周血中浓度较低。有人提出，分离、体外培养和鉴定 CTC 可能为非侵入性监测个体患者肿瘤获得新突变时药物敏感性的变化模式提供机会。在一项概念验证研究中，我们从六名雌激素受体阳性乳腺癌患者中建立了 CTC 培养物。在五只 CTC 系中，有三只在小鼠中具有致瘤性。对 CTC 系的基因组测序揭示了 PIK3CA 基因中存在预先存在的突变，以及雌激素受体基因 (ESR1)、PIK3CA 基因和纤维母细胞生长因子受体基因 (FGFR2) 等基因中获得的新突变。对具有多种突变的 CTC 系进行药物敏感性测试，揭示了潜在的新治疗靶点。通过优化 CTC 培养条件，这种策略可能有助于在患者疾病过程中为个别癌症患者确定最佳治疗方法。
