Left: GFP labeled metastases to bone (femur) and brain and CTCs from ER+ breast cancer PDX. Right: TSNE plot of sc RNA-seq of primary tumor, and bone and brain metastatic cells.
Mechanisms of ER+ breast cancer metastasis
Patients treated for ER+PR+ breast cancers are at continuous risk of recurrence for up to 20 years despite the use of adjuvant endocrine therapies and CDK4/6 inhibitors. Most often, metastases first appear in the bone marrow. Cells eventually escape and reside in vital organs. We are interested in learning how long term estrogen withdrawal remodels dormant tumor cells’ ability to survive as circulating tumor cells (CTCs). To study this, we are using our ER+ breast cancer models in conjunction with clinical specimens to study tumor cell changes that favor cell portability. Our long-term goal is to understand how the hormone milieu regulates ER+ and ER− subpopulations, and how intrinsic features of ER−/low/CSCs cells contribute to tumor progression.