Advancements in 3D Cell Culture Systems for Personalizing Anti-Cancer Therapies

Abstract

Over 90% of potential anti-cancer drug candidates results in translational failures in clinical trials. The main reason for this failure can be attributed to the non-accurate pre-clinical models that are being currently used for drug development and in personalised therapies. To ensure that the assessment of drug efficacy and their mechanism of action have clinical translatability, the complexity of the tumor microenvironment needs to be properly modelled. 3D culture models are emerging as a powerful research tool that recapitulates in vivo characteristics. Technological advancements in this field show promising application in improving drug discovery, pre-clinical validation, and precision medicine. In this review, we discuss the significance of the tumor microenvironment and its impact on therapy success, the current developments of 3D culture, and the opportunities that advancements that in vitro technologies can provide to improve cancer therapeutics.

ALTEN: A High‐Fidelity Primary Tissue‐Engineering Platform to Assess Cellular Responses Ex Vivo

“…These biomimetic matrices have been widely used as scaffolds to recreate 3D cellular structures, enabling in vitro studies of cell interactions with ECM components. [ 20 ] Here we have harnessed the properties of alginate matrices to preserve whole tissue pieces for ex vivo culture. ALTEN creates a permeable alginate sphere that preserves the original tissue architecture, cellular diversity, and ECM.…”

“…Currently, most perturbation screens are performed using conventional in vitro methods such as cell lines and more recently organoids; however, these methods have a limited capacity to recapitulate specific complex cellular niches in vivo (recently reviewed in ref. [ 2 ]). Cell lines and two‐dimensional (2D) in vitro coculture systems inherently lack heterogeneity and a tissue microenvironment and exhibit poor predictive power of the biological effects of specific stimuli or perturbations.…”

“…[ 5 ] Importantly, alginate does not activate any receptors on mammalian cells, and medical‐grade alginate has low immunogenicity, [ 6 ] making it an ideal substrate material for maintaining immune cell populations and assessing their ex vivo cellular responses. [ 2 ] Thus, unlike other materials that may be naturally found in the ECM, alginate does not alter the composition of the original ECM components allowing accurate representation of intact cellular niches.…”

Precision-Cut Tumor Slices (PCTS) as an Ex Vivo Model in Immunotherapy Research

“…The formation of intricate 3D tumor architecture in vivo allows for cell-to-cell interaction and signaling, resulting in advanced resistance to treatment [ 3 ]. Thus, the effect of different anti-tumor agents can often be significantly weaker in 3D tumors compared to 2D monolayers [ 6 , 7 ].…”

“…The culture of tumor cell lines in specialized collagen or other gel-like matrices allows for tumor cells to obtain a more 3D, spherical-like shape [ 3 , 8 , 9 ]. These 3D tumor “spheroids” are relatively easy to maintain in culture and can be more accurately used in drug treatment assays [ 7 ]. Nonetheless, both 2D and 3D cell line-based tumor models lack the in vivo tumor heterogeneity, where different cells within the same tumor site can have quite distinct and diverse genetic, epigenetic, phenotypic and tumor antigen expression profiles.…”