Projects per year
Our current research focus within the Cancer Studies group is spread across the following key areas:
Prostate cancer is distressingly common (diagnosed in 12% of men) and often fatal (9% of male cancer deaths). It is difficult to manage clinically due to a poor current understanding of what dictates its highly variable natural history. Treatment of early prostate cancer, with surgery or radiotherapy, should ideally be targeted to men with significant cancers, so that the remainder, with biologically 'irrelevant' disease, are spared the side-effects of treatment that includes impotence in a significant proportion of cases. We are analyzing biomarkers in exosomes prepared from patient urine in patients from the Norfolk and Norwich University Hospital. If the tests are successful they will provide a new test for detecting prostate cancer and for distinguishing aggressive from non-aggressive disease.
Whole Hospital DNA Sequencing
This project aims at collecting DNA mutation data and linked clinical data, from patients diagnosed with cancer at the Norfolk and Norwich University Hospital: in practice we are aiming eventually to collect gene mutation data for 350 cancer genes from 1200 cancers annually. We are initially focusing on the analysis of prostate cancer, lung cancer, colon cancer and breast cancer.
The In Silico Cancer Genetics Team research interests lie in applying and developing novel analytic techniques to large-scale genomic and expression datasets from human tumour samples to answer clinically relevant questions in translational cancer research. We are currently working on two major projects: The ICGC UK prostate project, a multi-centre collaboration that aims to collect and analyse the whole genome sequence of 250 prostatectomy prostate cancer samples and their matched blood, and the Whole Hospital DNA Sequencing, that aims to integrate mutational data with clinical factors and outcome to optimise the treatment of patients.
Together with Professor Richard Mithen at the Institute of Food Research we are investigating the ability of glucosinolates found in broccoli to slow or prevent prostate cancer development. Inside each of our cells are specialized structures called mitochondria, which produce energy. In prostate cell mitochondria are overloaded particularly when the cell are exposed to long chain fatty acids such as those present in meat and high levels of reactive oxygen species are generated. We believe that these effects can be reversed by broccoli consumption and that broccoli consumption will prevent prostate cancer development. We have won a grant awarded for $1million from the Prostate Cancer Foundation(USA) to investigate whether this idea is true.
Sphingosine kinase 1 (SK1) is an oncogenic enzyme that is highly expressed in human prostate tumours and has been shown to act as a "signalling hub" mediating cancer progression, angiogenesis and cell migration. Recent studies in prostate cancer have shown significant chemo- and radiosensitising potential of SK1 inhibition, specifically in combination with docetaxel chemotherapy, where silencing SK1 decreases cancer cell migration and invasion in cell and animal prostate cancer models. In this project we aim to develop a targeted "nanoparticle within nanoparticle" system for multi-component drug delivery (synergistic combination of novel SK1 inhibitors and docetaxel chemotherapy) to provide a new chemotherapeutic modality for patients with hormone refractory/chemoresistant metastatic prostate cancer.
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1/02/21 → 31/01/24
1/01/21 → 30/06/22
Allosteric site on SHIP2 identified through fluorescent ligand screening and crystallography: a potential new target for interventionWhitfield, H., Hemmings, A. M., Mills, S. J., Baker, K., White, G., Rushworth, S., Riley, A. M., Potter, B. V. L. & Brearley, C. A., 8 Apr 2021, In : Journal of Medicinal Chemistry. 64, 7, p. 3813–3826 14 p.
Research output: Contribution to journal › ArticleOpen AccessFile1 Citation (Scopus)2 Downloads (Pure)
Wang, Q., Bao, Y. & Chao, Y., 11 Feb 2021, In : RSC Advances. 11, 13, p. 7280-7293 14 p.
Research output: Contribution to journal › ArticleOpen AccessFile5 Downloads (Pure)
Conformation-specific inhibitory anti-MMP-7 monoclonal antibody sensitizes pancreatic ductal adenocarcinoma cells to chemotherapeutic cell killMohan, V., Gaffney, J. P., Solomonov, I., Levin, M., Klepfish, M., Akbareian, S., Grünwald, B., Dym, O., Eisenstein, M., Yu, K. H., Kelsen, D. P., Krüger, A., Edwards, D. R. & Sagi, I., 2 Apr 2021, In : Cancers. 13, 7, 1679.
Research output: Contribution to journal › ArticleOpen AccessFile3 Downloads (Pure)