Patient-derived 3D Models as a Novel Tool for Drug Developing and Testing

o Introduction

The process from drug discovery and development to commercialization and medical application is very long, complex, expensive and inefficient. Only about 8% of the drugs that are reaching clinical phase I trials will be successfully commercialized in the end. Therefore, there is an urgent need to develop assays and methods that can reliably predict the efficiency and usability of a drug under in vivo conditions during clinical trials. Using in vitro systems for drug development and testing has the advantages of avoiding ethical issues, as well as being more cost-effective than in vivo animal models. However, the 2D cell culture models cannot accurately mimic the complex response of an organ to anti-cancer treatments. That is the reason why around 95% of the anti-cancer drugs that showed a promising and potential response in 2D monolayers, failed during the clinical trials. In recent years, many systems have thus been created, and a growing number of research studies have been conducted in order to establish the usage of 3D tissue culture models.

o Material and method

One elegant and promising approach to build patient-derived 3D models is the microtissue culture system from InSphero AG (Switzerland) that provides functional 3D spheroids in a scaffold-free system. These 3D microtissue models present more accurately the physiological conditions in vivo. Here we used biopsy samples from breast (and anal) cancer patients, generated in vitro 3D models, applied a panel of chemotherapy drugs, and measured the cellular viability of the microtissue.

o Results and discussion

We were able to establish a well-working protocol for the generation of patient-derived 3D models in vitro. Due to the higher organization of cells grown in 3D systems (as compared to 2D monolayers), the testing of drugs on the 3D models better reflects the effect of irradiation, physical or chemical treatment on the micro-environment of the tissues regarding e.g. the access to nutrients, oxygen, growth factors, metabolites and paracrine factors.

o Conclusion

3D cell culture models present an ideal tool for drug developing and testing, and for a more accurate and reliable prediction of the therapeutic outcome on tumor growth.