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Full NameDavid John James Waugh
Department:Centre for Cancer Research and Cell Biology
Organisation:Queen's University Belfast
Postgrad Medical Specialties
I. Research Description (200 words max; Current = 166)
The overarching research interest of the group is to investigate the role of inflammatory chemokine signalling in the pathogenesis of prostate cancer and apply that knowledge to understanding resistance mechanisms to current treatment options and develop novel therapeutic strategies to improve patient outcomes. We have characterized the relationship between the pro-inflammatory chemokine interleukin-8 (IL-8) where we have shown that its expression becomes de-regulated during the early stages of disease with optimal expression in castrate-resistant disease. IL-8 signalling has been shown to potentiate numerous signalling pathways, culminating in the activation of several key transcription factors in the cancer cells (e.g. NFkB, HIF-1). Further work focuses on understanding critical resistance pathways associated with insensitivity to hormonal therapy and has identified the benefit of co-targeting the inflammatory microenvironment with hormonal therapy to optimize efficacy and duration of response in preclinical models. Overall, with these research projects we anticipate that our research will reveal new ways to overcome the problem of current treatment resistance and improve therapeutic options and responses.
Our pre-clinical research indicates that the addition of dual targeting of angiogenesis and inhibition of IL8 signalling to current hormonal therapy improves duration of response. Further research will seek to understand the impacts of these combinations in additional models to castrate-resistant prostate cancer. We will seek to determine further insights into the mechanism by which these agents may reverse castrate-resistance. In addition, we will seek to determine whether this mechanism is common to use of abiraterone or AR-targeting agents like enzalutamide. To determine the clinical relevance of these findings we will monitor patients on hormone therapy and analyse whether levels of these specific cytokines and growth factors correlate with response and/or development of resistance. If substantiated, our intent will be to translate this knowledge to write a new critical trial protocol.