Table 1.

A comparison of two-dimensional and three-dimensional models is shown [51]

SL no	Characteristics	Two dimensional	Three dimensional	References
1	Tumoral heterogeneity	The most fundamental; all cells receive the same quantity of nutrition. Misrepresentation of the TME during replication	Improved estimate and depiction of the tumor microenvironment; nutrients are not distributed evenly throughout the tumor	[52, 53]
2	Cell interactions	There are no cell niches formed when cells do not interact with one another or with the ECM	Cell junctions are widespread and enable for cell communication to take place between cells	[54–56]
3	Response to stimuli	Mechanical and biological inputs are inaccurately represented in the model	Cells develop in a three-dimensional environment and receive stimuli from all directions that are accurate representations of the stimuli they would experience in the environment	[57, 58]
4	Cost	Large-scale investigations are more affordable	Techniques that are more difficult and expensive	[59–61]
5	Cell differentiation and proliferation	Poor cell differentiation and unusually fast proliferation are observed	The proliferation of the cells is realistic and dependent on the interactions of the three-dimensional matrix	[54, 62–64]
6	Reproducibility	Highly repeatable	It is difficult to repeat several of the results	[6, 65]
7	Analysis and quantification	Results are simple to comprehend, and long-term cultures are preferable	Data analysis is difficult with various cell types or spheroid/organoid structures	[46, 51, 66]
8	Gene expression	Genes associated with cell adhesion; proliferation and survival are often altered	Representational accuracy of gene expression patterns	[67, 68]