ABSTRACT
Carcinogenesis is clearly a heterogeneous and complex biological process that can be described in multiple ways-transcriptional, molecular, histologic, clinical, to name a few. Adding to this complexity, this past decade has revealed the enormous heterogeneity in genetic and epigenetic events that can be used to describe this dysregulated growth of a normal cell into a tumor cell. Throughout this complex process, clearly, the key clinical turning point in carcinoma progression is the establishment by emigrant cells of secondary growth sites, i.e., metastases, which take up residence distant from the primary site of tumor origin. Carcinogenesis undergoes multiple steps to establish the primary tumor; and there are many additional steps needed to establish a metastatic tumor. This “metastatic cascade” that results in tumor spread can be described by a few critical, but discrete steps (Fig. 1) (21,49).
