You are here

Science DOI:10.1126/science.1253533

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

Publication TypeJournal Article
Year of Publication2014
AuthorsYu, 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, A Iafrate, J, Benes, C, Toner, M, Maheswaran, S, Haber, DA
JournalScience
Volume345
Issue6193
Pages216-20
Date Published2014 Jul 11
ISSN1095-9203
KeywordsAnimals, Antineoplastic Agents, Breast Neoplasms, Cell Culture Techniques, Cell Separation, Culture, Drug Resistance, Neoplasm, Drug Screening Assays, Antitumor, Estrogen Receptor alpha, Female, Gene Frequency, Humans, Mice, Microfluidics, Molecular Targeted Therapy, Mutation, Neoplastic Cells, Circulating, Phosphatidylinositol 3-Kinases, Sequence Analysis, DNA, Tumor Cells, Cultured, Xenograft Model Antitumor Assays
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.

URLhttp://www.sciencemag.org/cgi/pmidlookup?view=long&pmid=25013076
DOI10.1126/science.1253533
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/25013076?dopt=Abstract

Alternate JournalScience
PubMed ID25013076
PubMed Central IDPMC4358808
Grant ListR01 CA129933 / CA / NCI NIH HHS / United States
EB008047 / EB / NIBIB NIH HHS / United States
U01 EB012493 / EB / NIBIB NIH HHS / United States
R01 EB008047 / EB / NIBIB NIH HHS / United States
CA129933 / CA / NCI NIH HHS / United States
/ / Howard Hughes Medical Institute / United States
/ / Wellcome Trust / United Kingdom
P41 EB002503 / EB / NIBIB NIH HHS / United States