Key Challenges To UK Toxicology Research

The toxicology community faces a number of challenges that require for their solution a high-level innovative scientific vision and the nationwide integration of toxicology-related research centres. Scientific challenges: The molecular pathways that are initiated in response to toxic insult following exposure to chemicals, radiation and biological agents are not well defined. Lack of understanding of these pathways contributes to adverse drug reactions, which has severely hampered new drug development such that the rate of drug attrition, and resulting cost to Industry and the UK economy, is very high. Previous work in this area has focussed on transcriptional changes. However, gene expression is controlled at post-transcriptional and post-translational stages: regulation at these levels is as important as the transcriptional changes that occur following toxic injury. Thus to date, we have incomplete data about the factors and pathways that control the cellular response to toxic stress. Further, there is little mechanistic insight into the initiation of certain disease types that result from cellular responses to endogenous toxins, as in neurodegenerative diseases associated with toxic protein accumulation. These latter disorders have significant medical, social and economic implications for the UK population as it ages. Finally, an incomplete understanding of cytotoxic responses, particularly in cancers, is associated with drug resistance and poor overall patient survival.