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

Min Yu(Howard Hughes Medical Institute), Aditya Bardia(Harvard University), Nicola Aceto(Harvard University), Francesca Bersani(Harvard University), Marissa W. Madden(Harvard University), Maria Donaldson Collier(Harvard University), Rushil Desai(Harvard University), Huili Zhu(Harvard University), Valentine Comaills(Harvard University), Zongli Zheng(Harvard University), Ben S. Wittner(Harvard University), Petar Stojanov(Broad Institute), Elena F. Brachtel(Harvard University), Dennis C. Sgroi(Harvard University), Ravi Kapur(Center for Orthopaedics), Toshi Shioda(Harvard University), David T. Ting(Harvard University), Sridhar Ramaswamy(Harvard University), Gad Getz(Broad Institute), A. John Iafrate(Harvard University), Cyril H. Benes(Harvard University), Mehmet Toner(Harvard University), Shyamala Maheswaran(Harvard University), Daniel A. Haber(Howard Hughes Medical Institute)
Science
July 10, 2014
10.1126/science.1253533
Cited by 910Open Access
Full Text

Abstract

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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