Fig. 2

a Schematic representation of spheroid variation in shape and size over time, reprinted with permission from [88] (b) Schematic representation of a multicellular 3D spheroid cell culture, reprinted with permission from [63] (c) Main characteristics of the spheroid model, which is composed of several functionally differentiated areas and layers resulting from the impaired distribution of nutrients and oxygen. Tumor cells composing the spheroids interact with each other, developing a well-organized spatial architecture characterized by differences in phenotypic, functional, and metabolic status, reprinted with permission from [88]