2014/07/10 by Min Yu, Aditya Bardia, Nicola Aceto +21 · 1 citation
Medicine · Biochemistry, Genetics and Molecular Biology · #Cancer Cells and Metastasis #Cancer Genomics and Diagnostics #PI3K/AKT/mTOR signaling in cancer
paper · doi:10.1126/science.1253533
openalex publication_date 2014/07/10 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.