The therapeutic potential of targeting drugs at transcription factors

The pivotal role of gene transcription in a plethora of biological processes indicates that transcription represents a suitable target for potential therapeutic intervention. Ultimately, the pathophysiology of numerous human disease processes must be understood in terms of changes in gene expression within relevant body cell types. There is mounting evidence that genetic variation in transcription factors and/or their binding-site sequences, as well as environmentally induced malfunctioning of these proteins, contribute to common multifactorial disorders including cancer, diabetes, ischaemic heart disease and neural disorders. Even in 'non-inheritable' infectious diseases, alterations of host-cell transcriptional regulation play an important role in pathogenesis. The enormous progress in understanding the mechanisms of transcriptional control offers hope for the development of a new generation of drugs. Such compounds could be specifically designed to modulate either the synthesis of transcription factors, the regulation of their activity by small-molecule bioligands or phosphorylation events, their interactions with activator/repressor proteins or their binding to DNA. Given the remarkable specificity of this approach, it is anticipated that these agents will provide superior tools for the prevention and treatment of a diverse panel of clinical disorders in the not too distant future.