Biology-Oncology, Astex Pharmaceuticals and Cancer Research UK Cancer Therapeutics Unit, the Institute of Cancer Research, London
Initiation of mRNA translation generally requires an initiation complex to recognise the cap structure (m7G) of mature mRNAs, and the formation of a multi-protein mRNA cap-binding complex. Binding of proteins to the m7G cap structure is the first step in translation of mRNA, and changes in levels of these proteins contributes to oncogenesis and tumour maintenance. Importantly, many oncogenic signalling pathways alter the rate of protein synthesis by stimulating m7G cap-binding- either directly by changing the expression of initiation complex members, or indirectly through regulation of complex formation and activity. I am using molecular, biochemical and cellular techniques to explore the potential of inhibiting protein synthesis at the initiation level as a therapeutic strategy in cancer.