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

The process from drug discovery and development to commercialization and medical application is long, expensive and inefficient. Only 8% of drugs that reach clinical phase I trials are commercialized. Thus, there is an urgent need to develop assays that reliably predict the efficacy and safety of a drug under in vivo conditions. In vitro systems have the advantages of avoiding ethical issues, as well as being more cost-effective than animal models. However, 2D cell culture cannot accurately mimic the complex response of an organ to anti-cancer treatments. A growing body of research is establishing the 3D tissue culture models in which the higher organization of cells allows for a more authentic model.

Here, we present a promising new protocol for building 3D models from patient derived tissue, and for accurately predicting the outcome of therapeutic interventions in vitro.

We utilized the elegant approach from InSphero AG (Switzerland) that builds functional 3D spheroids in a scaffold-free system. Using biopsy samples from breast, prostate, esophagus, stomach, anal, and skin cancer patients, we generated 3D models in vitro. We validated the similarity of the microtissues to the original tumor using immunohistochemistry. Furthermore, we applied a panel of chemotherapy drugs, and measured the cellular viability of the microtissue in response.

We were able to establish an effective, working protocol for the generation of patient-derived 3D models in vitro. The microtissues are characterized as similar to the original tissue, and effectively predict the response of the tumor to various chemotherapeutic treatments.