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

نویسندگان

  • Min Yu
  • Aditya Bardia
  • Nicola Aceto
  • Francesca Bersani
  • Marissa W Madden
  • Maria C Donaldson
  • Rushil Desai
  • Huili Zhu
  • Valentine Comaills
  • Zongli Zheng
  • Ben S Wittner
  • Petar Stojanov
  • Elena Brachtel
  • Dennis Sgroi
  • Ravi Kapur
  • Toshihiro Shioda
  • David T Ting
  • Sridhar Ramaswamy
  • Gad Getz
  • A John Iafrate
  • Cyril Benes
  • Mehmet Toner
  • Shyamala Maheswaran
  • Daniel A Haber
چکیده

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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عنوان ژورنال:
  • Science

دوره 345 6193  شماره 

صفحات  -

تاریخ انتشار 2014