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

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

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Cell Culture Techniques
  • Cell Separation
  • Class I Phosphatidylinositol 3-Kinases
  • Culture
  • Drug Resistance, Neoplasm / genetics*
  • Drug Screening Assays, Antitumor / methods
  • Estrogen Receptor alpha / genetics
  • Female
  • Gene Frequency
  • Humans
  • Mice
  • Microfluidics / methods
  • Molecular Targeted Therapy*
  • Mutation
  • Neoplastic Cells, Circulating / drug effects*
  • Neoplastic Cells, Circulating / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Sequence Analysis, DNA
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • Estrogen Receptor alpha
  • estrogen receptor alpha, human
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human

Associated data

  • GEO/GSE51827
  • GEO/GSE55807