Transcending toward Advanced 3D-Cell Culture Modalities: A Review about an Emerging Paradigm in Translational Oncology

Cancer is a disorder characterized by an uncontrollable overgrowth and a fast-moving spread of cells from a localized tissue to multiple organs of the body, reaching a metastatic state. Throughout years, complexity of cancer progression and invasion, high prevalence and incidence, as well as the high rise in treatment failure cases leading to a poor patient prognosis accounted for continuous experimental investigations on animals and cellular models, mainly with 2D- and 3D-cell culture. Nowadays, these research models are considered a main asset to reflect the physiological events in many cancer types in terms of cellular characteristics and features, replication and metastatic mechanisms, metabolic pathways, biomarkers expression, and chemotherapeutic agent resistance. In practice, based on research perspective and hypothesis, scientists aim to choose the best model to approach their understanding and to prove their hypothesis. Recently, 3D-cell models are seen to be highly incorporated as a crucial tool for reflecting the true cancer cell microenvironment in pharmacokinetic and pharmacodynamics studies, in addition to the intensity of anticancer drug response in pharmacogenomics trials. Hence, in this review, we shed light on the unique characteristics of 3D cells favoring its promising usage through a comparative approach with other research models, specifically 2D-cell culture. Plus, we will discuss the importance of 3D models as a direct reflector of the intrinsic cancer cell environment with the newest multiple methods and types available for 3D-cells implementation.