Objective
Five year survival rates for breast cancer have shown strong improvements in recent years due to the
successful identification of new and improved therapies. However, triple
negative breast cancer (TNBC) has proved challenging to target therapeutically,
and is therefore associated with a significantly poorer prognosis compared to
other breast cancer subtypes. In order to identify small
molecules that preferentially target TNBC, two complementary imaging platforms
were used to perform multiplexed assays of cell apoptosis and viability. The IncuCyte
ZOOM system allows real time kinetic monitoring of cells, while the ImageXpress
Micro Confocal platform is a high content confocal imaging system suitable for high-throughput
screening applications. Using the LOPAC
1280 compound library, a
screen was undertaken that measured cell apoptosis and viability in breast
cancer cell models. Approximately 2% of the compound library was found to
preferentially induce apoptosis in TNBC cells compared to luminal A breast
cancer cells. The hits included compounds known to modulate hedgehog and FGF
signalling.
This study demonstrates the application
of multiplexed assay formats on complementary imaging platforms for compound screening
projects. This approach successfully identified potential drug targets and
pathways specific to TNBC cells, and is suitable for application across diverse
disease areas.