It is well established that cancer is a progressive disease, occurring in a series of well-defined steps, typically arising as a consequence of activating mutations (oncogenes) or deactivating mutations (tumor suppressor genes) in proliferating cells. From studies exploiting cultured tumor cells, two-stage carcinogenesis protocols in mice, and transgenic models of tumorigenesis, it is now evident that a single mutagenic event does not result in formation of a malignant tumor 1. Additional genetic and epigenetic events are necessary for progression to the tumor state. Initiated cells therefore require alterations rendering them self-sufficient for growth, insensitive to growth-inhibitory signals, resistant to programs of terminal differentiation, senescence, or apoptosis, as well as endowing them with unlimited self-renewal capacity, the ability to orchestrate and direct sustained angiogenesis, and the ability to invade and thrive in ectopic tissue environments 1. In this...

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