In vitro models: Can they unravel the complexities of cancer cell metastasis?

Metastasis still accounts for the majority of cancer-related deaths despite intense research efforts made worldwide to better understand the determinants involved and discover novel ways to halt it. However, studying the pathogenesis of metastasis in actual patients is indeed challenging which renders the need for the development of relevant experimental models urgent. Traditionally, several in vitro and in vivo models have been developed to study metastasis each of which having its own advantages and limitations. In the present review, we analyzed the current approaches used in cancer biology research to study cancer cell metastasis giving emphasis on the newly developed in vitro systems that take into account factors like the three-dimensional (3D) nature of the tumor, the interaction between cancer cells and the extracellular matrix or other cells present in the tumor microenvironment, and thus, better recapitulate the metastatic process. These approaches, namely 3D bioprinting, 3D tissue models, microfluidics systems, and spheroid generation are currently used separately or in combination depending on the research question and the cancer type in order to better represent the actual in vivo setting.