As essentially every breast cancer death is caused by metastasis, there is a fundamental need to understand the mechanisms of metastasis and to develop therapeutic strategies to inhibit this process. These researchers hypothesize that cCAFs (circulating Cancer Associated Fibroblasts) in clusters with circulating tumor cells (CTCs) are critical facilitators of breast cancer metastasis. Their overall goal is to understand the role of cCAF/CTC clusters in establishing breast cancer metastasis and to identify key genes expressed by these clusters, which may then be used for targeted therapy. Preliminary data show that cCAFs support cancer metastasis by inducing stemness and inhibiting endogenous immune responses. The researchers are also interested in evaluating the role of insulin and insulin-like growth factor (IGF) signaling in supporting these circulating clusters. There are two specific aims to test this hypothesis:
- Identify the molecular players that enable cCAF/CTC co-clusters to promote/maintain BC stemness and to modulate immune suppression
- Characterize the IGF signaling pathway in cCAF/CTC co-clusters as a mediator of survival, dissemination, and stemness phenotypes in breast cancer