GRB2 signaling as a molecular target for cancer

Adaptor proteins are key regulators of intracellular signaling. Many aspects of their functions have been elucidated and the structures of many members of this family of proteins have been resolved. The adaptor protein Grb2 is a critical component of the cell signaling machinery that is deregulated in several pathological processes, including cancer. A plurality of interactions make Grb2 an important cellular hub linking activated cell surface receptors to downstream targets by binding to specific phosphotyrosine-containing and proline-rich sequence motifs. Its critical roles in epithelial morphogenesis and in processes such as proliferation, actin-based cell motility, invasion, and angiogenesis make it a logical therapeutic target for several pathological processes, including human cancer. In this chapter Grb2 will be used as a paradigm to illustrate how adaptor proteins are involved in cancer and how it is possible to selectively target adaptor proteins for cancer therapy.