Circulating Tumor Cells Culture Promises Individualized Testing and Treatment

Yu et al in their paper in Science report that ex-vivo culture of breast circulating tumor cells (CTC) collected from patients over the course of their treatment allows for individualized treatment.   The researchers drew blood from women with breast cancer, isolated cancer cells in their blood, and tested which drugs might effectively halt the cancer. The technique consists of applying a magnetic coating on white blood cells and use magnets to select out the tumor cells for testing. These cells could then be used to grow tumors in laboratory dishes and in mice.  In their proof-of-concept study, they established CTC cultures from six patients with estrogen receptor–positive breast cancer. Three of five CTC lines tested were tumorigenic in mice.  Circulating tumor cells were present at low concentrations in the peripheral blood of those patients.  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. The method needs to be refined as only six out of 36 samples with breast cancer could be successfully grown in a dish.  It has been proposed that ex vivo culture and characterization of CTCs may provide an opportunity to noninvasively monitor the changing patterns in individual patients as their tumors acquire new mutations.  The authors suggest that drug sensitivity testing of CTC lines with multiple mutations revealed potential new therapeutic targets. With optimization of CTC culture, this strategy may help identify the best therapies for individual patients with cancer over the course of their disease with a simple blood draw instead of performing invasive biopsies or imaging studies that can be non-specific.  As cancer treatments require continuous adjustments oncologists need a noninvasive way to collect tumor cells from patients over the course of the treatment and decide when to replace a drug that worked initially but lost its potency as the tumor acquired new mutations. If the method becomes reliable and can be used to to grow cells from other types of cancer it has the potential to become a major advance in clinical oncology.