title: The application of 3D cell models to support drug safety assessment: opportunities & challenges.
abstract: The selection of drug candidates early in development has become increasingly important to minimize the use of animals and to avoid costly failures of drugs later in development. In vitro systems to predict and assess organ toxicity have so far been of limited value due to difficulties in demonstrating in vivo-relevant toxicity at a cell culture level. To overcome the limitations of single-cell type monolayer cultures and short-lived primary cell preparations, researchers have created novel 3-dimensional culture systems which appear to more closely resemble in vivo biology. These could become a key for the pharmaceutical industry in the evaluation of drug candidates. However, the value and acceptance of those new models in standard drug safety applications have yet to be demonstrated. This review aims to provide an overview of the different approaches undertaken in the field of pre-clinical safety assessment, organ toxicity, in particular, with an emphasis on examples and technical challenges.
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharma Research, 4070 Basel, Switzerland.
authors.forename: Adrian
authors.initials: A
authors.lastname: Roth
authors.affiliation: F. Hoffmann-La Roche Ltd., Pharma Research, 4070 Basel, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Singer
mesh_terms: D000818:Animals; D018929:Cell Culture Techniques / Q000379:methods* / Q000639:trends; D018920:Coculture Techniques; D055808:Drug Discovery / Q000379:methods* / Q000639:trends; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis / Q000517:prevention & control; D020869:Gene Expression Profiling / Q000379:methods / Q000639:trends; D022781:Hepatocytes / Q000187:drug effects / Q000502:physiology; D006801:Humans
keywords: 3R; Drug safety assessment; In vitro toxicology; Mechanistic toxicology; Predictive toxicology