Cultured CTCs reveal genetic profile, potential drug susceptibility of breast cancer cells

Circulating tumor cells captured with a microchip-based device developed at the Massachusetts General Hospital (MGH) Center for Engineering in Medicine and the MGH Cancer Center can be cultured to establish cell lines for genetic analysis and drug testing. In a recent issue of Science, an MGH research team reports that the cultured cells accurately reflect a tumor's genetic mutation over time and changing susceptibility to therapeutic drugs.

“We now can culture cells from the blood that represent those present in metastatic deposits, which allows testing for drug susceptibility as the tumor evolves and acquires new mutations,” says Shyamala Maheswaran, PhD, co-senior author.”We need to improve culture techniques before this is ready for clinical use, and we are working on doing that now.”

Circulating tumor cells (CTCs) break off from either a primary or metastatic tumor and are carried through the bloodstream in extremely small quantities. The current version of the MGH-developed device, called the CTC-iChip, does not rely on prior identification of marker proteins on the surface of tumor cells, a limitation of previous versions of the MGH device. Cell-surface proteins can change as tumors mutate during metastasis or in response to treatment, raising the possibility that methods targeting specific proteins may not reveal the full spectrum of CTCs.

The current study was designed to verify the ability of the CTC-iChip to capture viable CTCs in a way that enables the establishment of cell lines that accurately represent the genetic status of all existing tumor sites and can be used for the testing of therapeutic drugs. The researchers first isolated CTCs from the blood of 36 patients with metastatic, estrogen-receptor-positive breast cancer. Long-lived cell lines were successfully established from CTCs of six patients, all of whom previously had received several courses of hormonal and other therapies. Subsequent samples taken from three of those patients were used to establish additional cell lines to track how the tumors changed during subsequent treatment. Read the study abstract.