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.

Keywords: 3D bioprinting; 3D culture systems; drug resistance prevention; extracellular matrix; microfluidics; personalised medicine; tumor microenvironment.

Figure 1

Advantages and disadvantages of drug development using different pre-clinical models and clinical trials. The physical features when using a pre-clinical model is crucial to ensure physiological relevance. 2D cell cultures is a widely adopted and well-established model that has been used consistently in drug discovery and high throughput screening. However, cancer cells cultured in 2D do not recapitulate the biology of an in vivo tumor and thus has very poor performance for clinical prediction. As such, the use of more complex models such as 3D cell culture and mice models has been more representative of clinical cases compared to 2D cell culture. However, the standardized implementation of these models for applications in high content screening and personalised medicine remains a challenge.

Figure 2

Physiological differences between 2D cell culture and 3D cell culture. Cells develop as a 2D monolayer adopt an apical-basal polarity when plated on a culture flask or a petri dish. The environment that cells are exposed to within the culture flask is a poor representation and does not accurately recapitulate physiological conditions. Comparatively, 3D cultures provide greater biological relevance and cellular response to perturbations are more reflective of in vivo.

Figure 3

Advantages and disadvantages of various 3D culture approaches. The key features of 3D culturing aim to improve the biomimicry and predictive value of pre-clinical models. Suspension cultures and scaffold-based approaches are easier to implement in the lab and upscale for high-throughput. Advancements in microfabrication technology such as microfluidic chips and 3D bioprinting have resulted in more complex and physiologically-relevant models that can be generated.