3D Cell Culture Models as Recapitulators of the Tumor Microenvironment for the Screening of Anti-Cancer Drugs

Abstract

Today, innovative three-dimensional (3D) cell culture models have been proposed as viable and biomimetic alternatives for initial drug screening, allowing the improvement of the efficiency of drug development. These models are gaining popularity, given their ability to reproduce key aspects of the tumor microenvironment, concerning the 3D tumor architecture as well as the interactions of tumor cells with the extracellular matrix and surrounding non-tumor cells. The development of accurate 3D models may become beneficial to decrease the use of laboratory animals in scientific research, in accordance with the European Union’s regulation on the 3R rule (Replacement, Reduction, Refinement). This review focuses on the impact of 3D cell culture models on cancer research, discussing their advantages, limitations, and compatibility with high-throughput screenings and automated systems. An insight is also given on the adequacy of the available readouts for the interpretation of the data obtained from the 3D cell culture models. Importantly, we also emphasize the need for the incorporation of additional and complementary microenvironment elements on the design of 3D cell culture models, towards improved predictive value of drug efficacy.

Cancer Three-Dimensional Spheroids Mimic In Vivo Tumor Features, Displaying “Inner” Extracellular Vesicles and Vasculogenic Mimicry

“…This is the reason why, in recent years, alternative 3D culture models are being developed. In cancer research, 3D models are considered as an intermediate model between 2D cultures and in vivo experiments, being able to represent more truthfully some characteristics of in vivo tumors, in terms of cell-to-cell and cell-to-extracellular matrix (ECM) contacts, cellular layered assembling, hypoxia, and gradients of nutrient, oxygen, and pH [ 22 , 23 , 24 ].…”

Pentagalloyl Glucose and Cisplatin Combination Treatment Exhibits a Synergistic Anticancer Effect in 2D and 3D Models of Head and Neck Carcinoma

“…In order to approach the tumor situation in vivo more closely, a 3D tumor spheroid model and viability protocol were established. Tumor spheroids represent the architecture of solid tumors in vivo, mimicking the tumor microenvironment observed in different tumor heterogenic cells [ 39 ]. Our study agreed with other studies that 3D tumor spheroids were more resistant to treatment than 2D monolayers [ 40 , 41 ].…”

Tumour growth: Bayesian parameter calibration of a multiphase porous media model based on in vitro observations of Neuroblastoma spheroid growth in a hydrogel microenvironment

“…We present a novel, low-cost, and accessible method for the rapid characterisation of 3D cell clusterization using microfluidic chips that allow the culture of NB cells on collagen-type I hydrogels. The potential impact of 3D cultures has strongly been emphasised previously, and authors have provided a variety of techniques for introducing 3D culture systems with the aim of attaining more reliable and comprehensive results [108]. Efforts to transfer the experiments to 3D have also been made in NB [109][110][111][112][113].…”