Targeting Collectivity to Eradicate Breast Cancer Metastasis
Abstract
The root cause of most breast cancer-related deaths is metastasis, the spread of cancer to distant organs. Recent research indicates that, in breast cancer as well as many other tumor types, circulating clusters of tumor cells are associated with therapy resistance, widespread metastases, and significantly worse prognosis. By learning more about these micrometastases, this proposal seeks to identify molecular vulnerabilities that can be used to eradicate them, thereby extending survival in patients with metastatic breast cancer. A major barrier to eradicating tumor cell clusters is that they are more resistant to cancer therapy. Thus, our first goal will be to test whether intra-cluster signaling, a “hand-shake” that happens inside clusters, promotes the survival and growth of cancer cells. We will dissect whether blocking this signaling can be used to eradicate tumor cell clusters and thereby extend survival from metastatic breast cancer. A second challenge is that how tumor cell clusters enter the bloodstream is not currently understood. Thus, in our second goal, we will create new mouse models to study tumor cell cluster dissemination. The translational impact of this goal will be to discover combinations of imaging and biomarkers to catch this process early in the clinic. Finally, our third goal will be to evaluate methods to generate tumor cell clusters from circulating tumor cells in therapy-resistant metastatic breast cancer patients. We will utilize circulating tumor cell (CTC)-derived clusters to predict resistance early and to test agents that are able to overcome this resistance. Importantly, for decades, the clonal expansion of individual tumor cells has been a cornerstone for development of cancer therapy; instead of targeting single cells, our work seeks to prevent tumor cells from cooperating – a new approach. We anticipate that these basic preclinical studies can be readily translated to prevent, monitor, and treat metastatic breast cancer.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810098
Entities
People
- Kevin M Cheung
Organizations
- Fred Hutchinson Cancer Center
- United States Army