Accurately defining whether a tumor is benign or malignant is critical in determining the most appropriate course of therapy and, consequently, clinical outcome. Benign tumors, which are characterized by hyperproliferating cells, can, in most cases, be effectively treated by surgical removal if the tumor is located in an accessible and nonessential site in the body. However, when a tumor becomes malignant – acquiring dysplasia, dedifferentiation, and metastatic properties – treatment becomes extremely difficult because of profound genetic and epigenetic changes in the tumor that counteract host defense mechanisms, as well as exogenously delivered therapeutics [1]. Additionally, effective delivery to metastatic lesions can be difficult and inefficient. This chapter focuses on the genes and their products that have been identified and shown to be involved in regulating metastasis.

Metastasis is a dynamic process in which a transformed tumor cell migrates from its initial site of origin and colonizes at new locations in the body. In the biological cascade of metastasis, distinct steps have been delineated [2, 3]:

1. (1) Tumor cells become less adherent to the surrounding stroma and are shed from the primary tumor.

2. (2) Tumor cells acquire motility, degrade the surrounding extracellular matrix, and invade into it.

3. (3) The tumor cells enter into the circulation and survive (these processes are characteristic of the “intravasation” component of metastasis).

4. (4) Tumor cells emerge from the circulation and attach and enter new tissue (these processes are characteristic of the “extravasation” component of metastasis).

5. (5) Tumor cells proliferate and generate new secondary colonies of cells that are dependent on formation of a new blood supply – the process of angiogenesis. To perform each specific task, specific proteins (gene products) are necessary.