Understanding how breast cancer spreads and to identify preventive strategies to improve patient outcomes.

Impact

The major cause of breast cancer deaths is metastasis, the process by which breast cancer cells invade distant organs and establish new tumors there. To prevent this process from occurring, researchers must first identify the mechanisms that drive it. Dr. Ewald is studying metastasis at the cellular and molecular level with the goal of discovering ways to both prevent and treat metastatic breast cancer (MBC). His findings may guide the development of new strategies to improve outcomes for women with MBC.

Progress Thus Far

Metastasis requires cancer cells to accomplish many different tasks: escaping the primary tumor, entering, and surviving within blood vessels, evading immune cells, and growing in an unfamiliar organ. Dr. Ewald’s research has shown that breast cancer cells typically accomplish these tasks as small groups of cells that are connected to each other by molecular “junctions” and found that the adhesive protein E-cadherin is required to form these junctions and for metastasis. In the past year, Dr. Ewald has further shown that tight junctions between cells prevent cancer invasion and spread, that their loss increases metastatic efficiency, and that E-cadherin plays a critical role in tumor cell survival that is independent of its role in cell adhesion.

What’s next

In the coming year, Dr. Ewald will further explore whether tight junctions are a critical defense against metastasis, which would support the clinical observation that breast tumors with low expression of tight junction proteins are more aggressive. In addition, Dr. Ewald will use genetic techniques to determine which protein binding partners of E-cadherin are essential to its role in cancer cell survival.