In vitro toxicity model: Upgrades to bridge the gap between preclinical and clinical research.

Eneko Madorran,Uroš Maver,Andraž Stožer,Sebastjan Bevc

doi:10.17305/bjbms.2019.4378

Abstract

The Centers for Disease Control and Prevention (CDC) provides extensive data that indicate our need for drugs to maintain human population health. Despite the substantial availability of drugs on the market, many patients lack specific drugs. New drugs are required to tackle this issue. Moreover, we need more reliable models for testing drug toxicity, as too many drug approval failures occur with the current models. This article briefly describes various approaches of the currently used models for toxicity screening, to justify the selection of in vitro cell-based models. Cell-based toxicity models have the best potential to reliably predict drug toxicity in humans, as they are developed using the cells of the target organism. However, currently, a large gap exists between in vitro cell-based approach to toxicity testing and the clinical approach, which may be contributing to drug approval failures. We propose improvements to in vitro cell-based toxicity models, which is often an insight approach, to better match this approach with the clinical homeostatic approach. This should enable a more accurate comparison of data between the preclinical as well as clinical models and provide a more comprehensive understanding of human physiology and biological effects of drugs.

Highlights

In 2016, the Centers for Disease Control and Prevention (CDC) recorded 883.7 million physician office visits in the United States (US)
Because too many drug approval failures occur with the current models for testing drug toxicity, we should improve the reliability of the available models
Cell-based toxicity models have the best potential to reliably predict drug toxicity in humans, as they are developed using the cells of the target organism

Summary

INTRODUCTION

In 2016, the Centers for Disease Control and Prevention (CDC) recorded 883.7 million physician office visits in the United States (US). Several different features of drug approval process should be addressed concurrently to improve its reliability, the authors of this review will focus on the gap between preclinical and clinical research in drug toxicity testing. Visual Abstract and discuss the differences between them, to justify the selection of in vitro cell-based models as the toxicity models with the best potential to reliably predict drug toxicity in humans. We will further discuss the most significant failures of drug approval process when predicting drug toxicity, where the differences between the models may contribute to these failures This overview is the basis on which we have developed improvements to in vitro cell-based toxicity models, presented in the subsequent sections. There are some limitations to the current in vivo toxicity models, especially considering the significant biological differences that exist between the human and other animal organisms [18]. The toxicokinetic characteristics of cell-based toxicity models should be compatible with those of the human organism

Evaluation

Limitations

CONCLUSION AND FUTURE PERSPECTIVES