Preclinical Testing Techniques: Paving the Way for New Oncology Screening Approaches

SIMPLE SUMMARY: Traditional preclinical testing, including 2D cell culture and animal models, often fails to accurately predict drug efficacy in humans, especially for oncology drugs, where drug candidates that enter clinical trials have very high failure rates. Advancements in biology and tissue engineering techniques allow researchers to evaluate drug candidates before human trials using 3D cell culture models that more closely resemble human tissues than 2D culture methods. These techniques can better mimic the patterns of drug diffusion, cell–cell signalling, and the presence of vasculature in tumours in vivo. Furthermore, the FDA Modernization Act 2.0 promotes the use of higher complexity in vitro models such as 3D cell cultures. By offering more accurate representations of human tissue, 3D culture platforms have the potential to enhance preclinical drug development and lead to safer and more effective cancer treatments. ABSTRACT: Prior to clinical trials, preclinical testing of oncology drug candidates is performed by evaluating drug candidates with in vitro and in vivo platforms. For in vivo testing, animal models are used to evaluate the toxicity and efficacy of drug candidates. However, animal models often display poor translational results as many drugs that pass preclinical testing fail when tested with humans, with oncology drugs exhibiting especially poor acceptance rates. The FDA Modernization Act 2.0 promotes alternative preclinical testing techniques, presenting the opportunity to use higher complexity in vitro models as an alternative to in vivo testing, including three-dimensional (3D) cell culture models. Three-dimensional tissue cultures address many of the shortcomings of 2D cultures by more closely replicating the tumour microenvironment through a combination of physiologically relevant drug diffusion, paracrine signalling, cellular phenotype, and vascularization that can better mimic native human tissue. This review will discuss the common forms of 3D cell culture, including cell spheroids, organoids, organs-on-a-chip, and 3D bioprinted tissues. Their advantages and limitations will be presented, aiming to discuss the use of these 3D models to accurately represent human tissue and as an alternative to animal testing. The use of 3D culture platforms for preclinical drug development is expected to accelerate as these platforms continue to improve in complexity, reliability, and translational predictivity.