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

Science
Authors
Keywords
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.

Year of Publication
2014
Journal
Science
Volume
345
Issue
6193
Pages
216-20
Date Published
2014 Jul 11
ISSN
1095-9203
URL
DOI
10.1126/science.1253533
PubMed ID
25013076
PubMed Central ID
PMC4358808
Links
Grant list
R01 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