Metastasis: A Major Driver of Cancer Pathogenesis

Cancer is a multifactorial condition that originates from genomic alterations in the cells, which confer them the ability to evade various cellular regulations and proliferate incessantly. Furthermore, the accumulation of these mutations confers metastatic abilities to the tumor cells, which help them in contriving various features essential for invasion of the host tissues and evading immune surveillance and thus spreading to distant sites. Metastasis is a key phenomenon in cancer pathogenesis, which involves invasion of host tissue, escape into the blood vascular system, survival within the circulation, extravasation into the secondary sites, establishment of micrometastasis, and colonization. The tumor cells utilize various host cells and pathways to reach the pre-destined sites, also known as pre-metastatic niches (PMNs). The primary tumor is known to secrete various factors, which render the secondary metastatic sites hospitable for the arriving tumor cells. These tumor cells, in turn, invade the PMNs and either undergo dormancy or outgrow to develop secondary metastases. Since metastasis involves a cascade of events, it also offers attractive targets for therapeutic intervention. This chapter elaborates the series of events involved in metastasis initiation and progression along with the role of PMNs and various therapeutic approaches to target metastasis.