Mechanisms of malignant progression

While a coherent picture has begun to emerge about the biological and molecular mechanisms that create primary tumors, the processes that lead subsequently to invasion and metastasis have, until recently, been relatively obscure. However, over the past 5 years, research of diverse sorts has begun to generate the conceptual outlines that explain how high-grade malignancies arise. These discussions invariably are motivated by a widely accepted depiction of how metastatic dissemination occurs—the sequence termed the ‘invasion–metastasis cascade’ (1). Thus, primary tumor cells invade locally, enter into the circulation (intravasation), are transported through the circulation, are lodged in microvessels in distant tissues, invade the parenchyma of such tissue (extravasation) and form micrometastatic deposits, some of which eventually grow into macroscopic metastases, the last process being termed colonization.