Making cell culture models more physiologically relevant

A major limitation in drug development is the occurrence of drug-candidate toxicity during clinical research. This may occur because tumour-derived cell lines are limited as a pre-clinical model – in part because of an altered metabolic poise. A recent study has revealed a profound plasticity in gene expression and metabolic poise that can be exploited by replacing glucose with galactose in the cell culture medium. Here, Robert Skolik, a researcher from the study, explains how the galactose‑induced cellular phenotype is more reminiscent of a primary hepatocyte, which may aid in the early detection of hepatotoxic compounds.

Cell line development image

Development of novel medications is becoming increasingly difficult and expensive. The average cost to bring a new drug to market is close to $1 billion and often takes over a decade. This is in part because nearly 88 percent of drugs reaching clinical trials fail to gain final US Food and Drug Administration (FDA) approval.1 Drug-induced toxicity is responsible for nearly half of these failures, despite extensive investment in pre-clinical toxicity screenings. The liver is most frequently affected by drug-induced toxicity, which is not surprising considering…

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