Abstract
Cancer is a multifactorial disease with cellular proliferative molecular networks and immune evasion properties. The well-known cancer intra- and inter-tumoral heterogeneity presents a notable limitation of the current histological and diagnostic techniques. Thus, biasing the risk of invasiveness and restricting its broader application in oncology in prognostic, survival, and treatment response differences between patients. Monolayer cell cultures have been a consistent in vitro model in cancer research throughout time. However, this system fails to replicate the complex pathogenesis of this disease, as key mechanisms underlying initiation, metastasis, drug resistance, and recurrence remain poorly understood. 3D culture models are presented as the most suitable model to better reflect the patient's tumor development. Some methods to introduce the third dimension into cell cultures is by promoting cell-cell interactions to give 3D cell structures, using scaffolds to promote growth beyond monolayers and introducing microfluidic platforms to the system. The present review provides an overview of different techniques to develop 3D culture models in oncology, the advantages compared between monolayer cell cultures, their applications, limitations, and applicability in oncology research. See also the graphical abstract(Fig. 1).