Most breast cancer deaths are from metastasis, rather than growth of the primary tumor. Therapies for reducing deaths from metastatic cancer are limited, in part because much of the basic biology of metastasis remains unknown. We are developing and applying methods to identify these basic mechanisms. We describe work with experimental and clinical partners using organoids, clusters of 300-500 primary mammary cells, to interrogate metastasis-related phenotypes. We present new mathematical image processing methods that convert organoid images into quantitative invasion phenotypes. We then discuss genes and pathways whose activities lead to invasion, dissemination, and metastasis. Often the driver and effector genes are poor candidates for therapeutic intervention, but signaling intermediates can be targeted. We are prioritizing intermediates using new methods that characterize the density of paths through a biological network. We are recruiting women with breast cancer to participate in these studies as part of our US NCI Cancer Target Discovery & Development (CTD2) Center.
