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Prof Robert Nicholson 


General

Member of the School's Pharmacology & Physiology Research Discipline

 

Cancer research within the School of Pharmacy and Pharmaceutical Sciences is multifaceted and includes projects designed to (i) understand the molecular basis of cancer and its treatment and (ii) exploit the information gained in novel drug design and delivery. In this context, I have two roles. Firstly, to co-ordinate the School’s Experimental Cancer Theme, bringing together those with an interest in cancer research to share and develop ideas which will hopefully translate into increased grant income. We are extremely well positioned in this respect with several academic and research staff having a primary research interest in cancer and this has already borne considerable fruit with a large research income being generated from Industry, Government and Charities. Secondly, I am also the current Director of the Tenovus Centre for Cancer Research whose principal objective is to understand drug resistance mechanisms in cancer cells in order to identify new targets for therapeutic exploitation. Our current focus is on understanding a new phenomenon recently identified by our group, that is drug induced compensatory signalling which we believe acts to limit the effectiveness of  many of the most important classes of drugs used in the therapy of cancer, including anti-hormones, anti-growth factors and signal transduction inhibitors.  

           

Research Interests

Increasingly, anti-cancer drugs are being targeted to the signalling pathways that are believed responsible for the aberrant features of cancer cells. Unfortunately, although these drugs often improve the outlook for cancer sufferers, all too frequently resistance arises and in some patients the benefits of drug treatment can be extremely short-lived. In the Tenovus Centre for Cancer Research in Cardiff, our philosophy is that if we can identify the complex mechanisms involved in the development of drug resistance, then we can use this knowledge to devise more intelligent therapeutic strategies to combat the cancer and significantly extend patient survival (Nicholson et al, 2007). Critically, recent experimental studies have highlighted a novel phenomenon-“drug-induction of compensatory signalling elements” that acts to (i) limit initial response to anti-oestrogen receptor (ER; Gee et al, 2006) and anti-epidermal growth factor receptor (EGFR; Hutcheson et, 2006) therapies, (ii) permit drug resistance to develop (Nicholson et al, 2007) and (iii) facilitate invasive behaviour and production of angiogenic factors (Gee et al, 2006). We believe that this phenomenon is likely to be shared by all current and future targeted therapies, where it may act to significantly reduce their effectiveness in patients. Increasingly, our knowledge in this area is allowing us to target such signalling and improve therapeutic response.

 

Several senior research scientists are involved in this work:

 

Collaborators

Internal

  • Dr Iain Hutcheson and Dr Mark Gumbleton: Caveolin 1 and breast cancer
  • Professor Chris McGuigan and Dr Andrew Westwell: Screening of novel cytotoxic drugs in cancer
  • Dr Andrea Brancale: Molecular design of novel signal transduction inhibitors

External

  • Dr Elizabeth Anderson (AstraZeneca, UK): Targeting of aberrant signalling in cancer cells
  • Professor Susan A Fuqua (Baylor College of Medicine, Houston, USA): Role of mitogen-activator protein kinase 3 in anti-hormone resistant breast cancer
  • Professor Charles Coombes and Dr Simak Ali (ICR, London)
  • Professor John F R Robertson and Professor Ian O Ellis (City Hospital, Nottingham, UK): Clinical and pathological studies in endocrine responsive and resistant breast cancer

 

Research Funding

  • Tenovus Cancer Charity
    Deciphering compensatory signalling promoted by anti-hormones in breast cancer £1,240,000 01/04/2007 – 31/03/2010.  Joint with Dr JMW Gee
  • AstraZeneca
    Drug response and resistance in breast cancer. £192,000 2006–2008. Joint with Dr JMW Gee.
    ER negative breast cancer: targeting the IGF-1R and beyond. £107,000. 01/07/2006 – 31/12/08. Joint with Dr JMW Gee.
  • Breast cancer Campaign
    Zinc signalling in anti-hormone resistant breast cancer cells. Joint with Dr KM Taylor. £14,790 26/01/07 – 25/06/07.
    CD44 mediated activation of c-met in ER-negative breast cancer cells.  £14,464 26/01/07 – 03/05/07. Joint with Dr SE Hiscox and Dr JMW Gee