Targeting alternative splicing as novel therapeutic approaches in cancer

SoMS, BABS and GSBE Cross-Faculty Seminar Series
David Bates, University of Nottingham
Abstract: The role of the vasculature in tumour progression and metastasis has for many years been focussed on two specific targets – delivery of nutrients or chemotherapeutic agents by blood flow, and the role of angiogenesis in the formation of new vasculature. Recently however, the role of the vasculature in delivering an immune response to the tumours has also come under scrutiny. The role of the microenvironment and angiogenesis in immune responses is now beginning to be unravelled, and applied in design of novel therapeutic strategies. One key driver of this interaction is the role of VEGF in and the potential to unlock immunotherapy through modulating VEGF is becoming clear. Alternative RNA processing of the VEGF-A pre-mRNA can result in anti-angiogenic isoforms, which counteract the angiogenic isoforms VEGF-A isoforms, such as VEGF-A165b. Manipulation of expression of these isoforms has now been identified as potential therapeutic approach in a number of different cancers including lung, blood, breast, colon and prostate cancers. The mechanisms underlying VEGF isoforms control include growth factor, environmental impacts such as hypoxia, and genetic factors. Identification of mechanisms that regulate anti-angiogenic VEGF expression has led to the development of inhibitors of key processes in that regulation, including phosphorylation of SRSF1 by SRPK1. Manipulation of VEGF-A165b expression by development of novel, potent, druggable SRPK1 inhibitors is a potential therapeutic approach in these cancers. Prof Bates’ seminar will cover how understanding regulation of alternative splicing has resulted in the identification of multiple cancer controlling pathway in the tumour microenvironment, and the development of novel therapeutic approaches.
Bio: David Bates is the Director of the Centre for Cancer Sciences, Head of the Cancer Research Priority Area, Director of Research and Chair of Strategy for the Division of Cancer and Stem Cells in the School of Medicine at the University of Nottingham, and Chief Scientific Officer of Exonate Ltd. He has discovered how new VEGFs contribute to age related macular degeneration, diabetic retinopathy, nephropathy and neuropathy, cancer, lung and heart disease and other conditions. He has 10 patents and >150 peer reviewed papers. 
Date & Time: Wednesday 22 November at 4.00 pm followed by Happy Hour.