The Roles of Ras Family Small GTPases in Breast Cancer

Members of the Ras subfamily of small GTPases may represent attractive targets for the treatment of breast cancer, but more research is needed to fully understand the roles these proteins play in breast cancer. Other small GTPases, including members of the Rho and Rab subfamilies, which are implicated in breast cancer, are reviewed. This chapter focuses on these Ras family proteins involved in breast cancer and on possible strategies to correct the cancer related defects in these proteins for breast cancer treatment. Currently, GTPases are not considered promising druggable targets. Since GTPases bind GTP with nanomolar to picomolar affinities, small molecule approaches to block GTP binding are not feasible. Recent work has revealed a mechanism by which H-Ras expression is elevated in breast tumor initiating cells, which may represent breast cancer “stem cells.” There are several other members of the Ras subfamily that have been implicated in breast cancer, but more studies are needed to determine the importance of these proteins in breast cancer. As strategies to therapeutically inhibit small GTPase signaling improve, it will be imperative to understand the contributions of each of these proteins to breast cancer development and progression.