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

Autor:	Yu M; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA., Bardia A; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Aceto N; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Bersani F; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Madden MW; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Donaldson MC; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Desai R; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Zhu H; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Comaills V; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Zheng Z; 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., Wittner BS; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA., Stojanov P; Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA., Brachtel E; Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA., Sgroi D; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA., Kapur R; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Shioda T; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Ting DT; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Ramaswamy S; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Getz G; 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., Iafrate AJ; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Pathology, Harvard Medical School, Charlestown, MA 02129, USA., Benes C; Massachusetts General Hospital Cancer Center, Harvard Medical School, Charlestown, MA 02129, USA. Department of Medicine, Harvard Medical School, Charlestown, MA 02129, USA., Toner M; Center for Bioengineering in Medicine, Harvard Medical School, Charlestown, MA 02129, USA. Department of Surgery, Harvard Medical School, Charlestown, MA 02129, USA., Maheswaran S; 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., Haber DA; 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.
Jazyk:	angličtina
Zdroj:	Science (New York, N.Y.) [Science] 2014 Jul 11; Vol. 345 (6193), pp. 216-20.
DOI:	10.1126/science.1253533
Abstrakt:	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. (Copyright © 2014, American Association for the Advancement of Science.)
Databáze:	MEDLINE
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