Ex vivo culture of circulating breast tumor cells for individualized testing of drug susceptibility

作者：Min Yu, Aditya Bardia, Nicola Aceto, Francesca Bersani, Marissa W. Madden, Maria Donaldson Collier, Rushil Desai, Huili Zhu, Valentine Comaills, Zongli Zheng, Ben S. Wittner, Petar Stojanov, Elena F. Brachtel, Dennis C. Sgroi, Ravi Kapur, Toshi Shioda, David T. Ting, Sridhar Ramaswamy, Gad Getz, A. John Iafrate, Cyril H. Benes, Mehmet Toner, Shyamala Maheswaran, Daniel A. Haber · 发表于：Science · 年份：2014 · DOI：10.1126/science.1253533 · 被引用次数：913 · 研究领域：Cancer Cells and Metastasis、Cancer Genomics and Diagnostics、PI3K/AKT/mTOR signaling in cancer

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.