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Science. 2014 Jul 11;345(6193):216-20. doi: 10.1126/science.1253533.

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

Author information

1
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
2
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
3
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA.
4
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medical Epidemiology and Biostatistics, Karolinska Insitutet, Stockholm, Sweden.
5
Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
6
Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA.
7
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA.
8
Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA.
9
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA. Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.
10
Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA.
11
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu.
12
Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA. maheswaran@helix.mgh.harvard.edu haber@helix.mgh.harvard.edu.

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.

PMID:
25013076
PMCID:
PMC4358808
DOI:
10.1126/science.1253533
[Indexed for MEDLINE]
Free PMC Article

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