FIGURE 1.

Framework for the development of in vitro models of metastatic dormancy. In vitro models should include one or more features of the dormant niche starting from measurements/observations of the target metastatic tissue in vivo. Then cellular systems have to be chosen based on clinical evidences that support their specific use, i.e., correct metastatic tropism, correct gene expression (when available), correct response to signals (such as inflammation). After the initial setup, the in vitro system must be validated and the cell lines, as well as the microenvironment, should exhibit one or more features specific of the dormant phenotype (obtained from animal models or clinical data). The in vitro system should then be exploited to generate hypothesis and prediction that could be tested experimentally in animal models or from clinical data. Finally, according to the feedbacks from the in vivo validation, the system can be refined for more accurate predictions and hypothesis.