Figure 2.

Mechanisms of induction of and escape from tumor dormancy. Tumor cells, when confronting a hostile environment, may enter a dormant state due to the interactions of extracellular factors (mainly hypoxia and immune cytotoxicity) and intracellular pathways. In response to signals that are not fully elucidated yet but appear to involve modifications of tumor microenvironment, such as extracellular matrix remodeling, neovascularization, chronic inflammation and tissue-specific mechanisms in each metastatic site, tumor cells escape from dormancy, start to proliferate and ultimately form macroscopic metastases in target organs. Abbreviations: ECM = Extracellular Matrix, ERK = Extracellular signalregulated kinase.