The inefficient translation from in vitro drug screening to preclinical and clinical studies is related to the use of 2D cell cultures in the first phases of preclinical studies.
In the last decades, over 80% of anticancer drug candidates entering phase I clinical testing have failed to reach the market in Europe. This inefficient translation from in vitro drug screening to preclinical and clinical studies is related to the use of two-dimensional (2D) cell cultures in the first phases of preclinical studies.
The good and the bad of 2D models
2D models are the gold standard method because they are cheap and easy to handle, but they do not present cell–cell and cell–matrix interactions occurring in native environment. Indeed, cells grow as a monolayer on a flat surface where almost half of the cell’s surface adhere to culture-grade plastic, while the other is immersed in culture medium, with only a little interaction with other cells. Both intercellular communication by contact and by paracrine mediators is tough, because the ‘organ context’ is ignored or because soluble signals are immediately diluted by cell culture medium.
Preclinical to clinical: animal models
Animal models are required to validate the results obtained from 2D cultures and to test bioavailability and toxicity. However, animal models are expensive and time-consuming. Moreover, genetic, metabolic, and ontogenetic differences exist between human and animal models, and usually murine tumours do not behave like human tumours. In addition, the use of animal models is ethically controversial.
There is an urge to develop new in vitro models
3D cultures could be useful for pre-in vivo screening during drug development. They allow the culture of cancer cells alone or with various cell types in a spatially relevant manner. Moreover, 3D cultures promote both cell–cell and cell–matrix interactions that closely resemble the native environment and it has been shown that cells in 3D present morphology and functional activities, such as signal transduction, gene and protein expression patterns similar to those observed in solid tumors. In addition, cells cultured in 3D were found to closely replicate drug diffusion observed in the in vivo scenario. Thus, the use of these models can be a useful tool to reduce the number of animal models exploited in tumour research.
As you can see, 3D in vitro models have been obtained as an innovative approach to integrate the results obtained from 2D cultures and to decrease the use of animal models. There are different kinds of 3D models and they can broadly be divided into two major classes: scaffold-free models and scaffold-based models. If you want to know more about their development and their use, follow us in the next posts!
Author: Dr. Bianca Bazzolo
Bibliography:
- Huang, Bu Wei and Jian Qing Gao. 2018. “Application of 3D Cultured Multicellular Spheroid Tumor Models in Tumor-Targeted Drug Delivery System Research.” Journal of Controlled Release 270(August 2017):246–59
- Sant, Shilpa and Paul A. Johnston. 2017. “The Production of 3D Tumor Spheroids for Cancer Drug Discovery.” Drug Discovery Today: Technologies 23:27–36.
