Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
Cancer therapy. Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility.
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DOI：
10.1126/science.1253533
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发表时间：
2014-07-11
期刊：
影响因子：
--
通讯作者：
Haber DA
中科院分区：
文献类型：
--
作者：
Yu M;Bardia A;Aceto N;Bersani F;Madden MW;Donaldson MC;Desai R;Zhu H;Comaills V;Zheng Z;Wittner BS;Stojanov P;Brachtel E;Sgroi D;Kapur R;Shioda T;Ting DT;Ramaswamy S;Getz G;Iafrate AJ;Benes C;Toner M;Maheswaran S;Haber DA
循环肿瘤细胞（CTC）以低浓度存在于实体瘤患者的外周血中。已经提出，CTC的分离、离体培养和表征可以提供一个机会，以非侵入性地监测个体患者的药物敏感性的变化模式，因为他们的肿瘤获得新的突变。在一项概念验证研究中，我们从6名雌激素受体阳性乳腺癌患者中建立了CTC培养物。测试的五个CTC系中的三个在小鼠中是致瘤性的。CTC细胞系的基因组测序揭示了PIK3CA基因中预先存在的突变以及雌激素受体基因（ESR1）、PIK3CA基因和成纤维细胞生长因子受体基因（FGFR2）等中新获得的突变。具有多个突变的CTC系的药物敏感性测试揭示了潜在的新治疗靶点。随着CTC培养条件的优化，这一策略可能有助于确定个体癌症患者在其疾病过程中的最佳疗法。
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.
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影响因子：
10.5
作者：
Dontu, G;Abdallah, WM;Wicha, MS
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Benes, Cyril H.
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8.8
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