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Drug Targeting & Transport

The focus of the Therapeutic Targeting and Transport Research Group is to increase our understand of - and so potential to improve - targeting with currently available drugs (including classical chemotherapeutics drugs, monoclonals and small molecules) while, in parallel, identifying and characterising novel companion therapeutic targets: predictive biomarkers for more precise, effective treatment design, transportation and delivery.

A significant problem with many currently available treatment regimes is a poor understanding of the treatment target(s), their mechanism(s) of transportation to site(s)-of-action, and cellular mechanism(s) of inherent or acquired resistance to such agents. This results in lack of both specificity and efficacy. For example, a serious challenge when treating cancers is maximising effects on cancer cells -to achieve the desired effect before the onset of resistance- while minimising damage to healthy tissues and organs. Recent advances in molecular biology and biotechnology are enabling the identification of many molecules directly associated with the development and progression of disease. Rational interpretation and exploitation of this information, together with application of more specific targeted drug delivery systems , has the potential to revolutionise treatment of disease in a more informed, regulated and defined way.

Head of Research Group

Members of the Research Group

TCD Collaborators

  • Dr. Ray McDermott, Consultant Oncologist, AMNCH, TCD
  • Dr. Michael Jeffers, Consultant Pathologist, AMNCH, TCD
  • Dr. Ken O'Byrne, Consultant Oncologist, SJH, TCD

National and International Collaborators

  • Dr. Mark Gumbleton (Cardiff University, UK)
  • Prof. Udo Bakowsky (Philipps University Marburg, Germany)
  • Dr. Susan Kennedy (Consultant Pathologist, SVUH/UCD, Ireland)
  • Prof. Martin Clynes (Director, NICB, Dublin City University)
  • Prof. John Crown (Consultant Oncologist, SVUH/UCD, Ireland)
  • Dr. Winfried Albert (Managing Director, Adnagen, Langenhagen, Germany)
  • Dr. Donal O'Shea (CEO, SlidePath, Dublin)
  • Dr. Stephen Hewitt (Director of Tissue Array Research Program, NCI/NIH, US)
  • Prof. Ken Anderson (Prof. of Medicine, Dana-Farber Cancer Institute, Harvard University, US)

Current Research Projects & Funding

Liposomal drug carrier systems for inhalation chemotherapy of lung cancer - Enterprise Ireland Proof of Concept Fund (€90,792). October 2007 - October 2008. PI Dr. Carsten Ehrhardt; Collaborators Prof. Marek Radomski, Dr. Anne Marie Healy

Characterisation of 2 Novel mRNAs present in breast tumours – but not in normal tissue- with potential as therapeutic targets & diagnostic/prognostic biomarkers. Health Research Board (€258,040). October 2006 – March 2010. PI Dr. Lorraine O'Driscoll

Current Relevant ICORG* Translational Clinical Trials

( *ICORG = Irish Clinical Oncology Research Group )

R McDermott, W Albert, M Clynes, L O'Driscoll: Circulating tumour cell biomarkers of response to taxotere in hormone-refractory prostate cancer

J Crown, R O'Connor, M Clynes, L O'Driscoll: Phase II trial of multi-drug resistance protein modulating agent sulindac in combination with epirubicin in patients with advanced melanoma.

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Selected Publications & Patents

H Bakowsky, T Richter, C Kneuer, D Hoekstra, U Rothe, C Ehrhardt , U Bakowsky. Adhesion characteristics and stability assessment of lectin-modified liposomes for site-specific drug delivery. Biochim Biophys Acta - Biomembranes , 1778:242-249, 2008

L O'Driscoll, E Kenny, JP Mehta, P Doolan, H Joyce, P Gammell, A Hill, B O'Daly, D O'Gorman, M Clynes . The feasibility and relevance of global expression profiling of gene transcripts in serum using whole genome microarrays. Cancer Genomics Proteomics 5: 95-104, 2008

S Kennedy, M Clynes, P Doolan, JP Mehta, J Crown, L O'Driscoll. SNIP/p 140Cap mRNA expression is an unfavourable prognostic factor in breast cancer and is not expressed in normal breast tissue. Br J Cancer 98: 1641-1645, 2008

E Hennessy , L O'Driscoll . Molecular medicine of microRNAs. Expert Rev Mol Med 10: 24-34, 2008

A Pierce , N Barron , R Linehan , E Ryan , C Daly, L O'Driscoll , M Clynes . Identification of a novel functional role for S100A13 in invasive lung cancer cell lines. Eur J Cancer 44:151-159, 2008

V Martinez, S Kennedy, P Doolan, P Gammell, H Joyce, E Kenny, JP Mehta, E Ryan, J Crown, M Clynes, L O'Driscoll. Drug metabolism–related genes as potential biomarkers: analysis of expression in normal and tumour breast tissue. Breast Cancer Res Treat 110: 521-30, 2007

R O'Connor , M Clynes, P Dowling, N O'Donovan, L O'Driscoll. Drug resistance in cancer - searching for mechanisms, markers & therapeutic targets. Exp Opin Drug Metab Toxicol 3 : 805-17, 2007

P Doolan, M Clynes, S Kennedy, JP Mehta, J Crown, L O'Driscoll. Prevalence and prognostic and predictive relevance of PRAME in breast cancer. Breast Cancer Res Treat 109: 359-365, 2007

P Dowling, L O'Driscoll, P Meleady, M Henry, S Roy, J Ballot, M Moriarty, J Crown, M Clynes. Two-dimensional difference gel electrophoresis of the lung squamous cell carcinoma v's normal sera demonstrates consistent alterations in the levels of 10 specific proteins. Electrophoresis 28: 4302-4310, 2007

S Endter, U Becker, N Daum, H Huwer, CM Lehr, M Gumbleton, C Ehrhardt. P-glycoprotein (MDR1) functional activity in human alveolar epithelial cell monolayers. Cell Tissue Res 328 (1):77-84, 2007

U Becker, C Ehrhardt, N Daum, C Baldes, UF Schaefer, K Rupprecht, KJ Kim, CM Lehr. Expression of ABC-transporters in human corneal tissue and the transformed cell line, HCE-T. J Ocul Pharmacol Ther 23 (2):172-181, 2007

S Roy, E Kenny, S Kennedy, A Larkin, J Ballot, M Perez de Villarreal, J Crown, L O'Driscoll MDR1/P-glycoprotein and MRP-1 mRNA and Protein expression in non-small cell lung cancer. Anticancer Res 27: 1325-1330, 2007

S Anabousi, U Bakowsky, M Schneider, H Huwer, CM Lehr, C Ehrhardt. In vitro assessment of transferrin-conjugated liposomes as drug delivery systems for the inhalation therapy of lung cancer. Eur J Pharm Sci 29 (5):367-374, 2006

C Kneuer, C Ehrhardt, M Radomski, U Bakowsky. Selectins - potential pharmacological targets? Drug Discov Today 11 (21-22):1034-1040, 2006

L O'Driscoll, J McMorrow, P Doolan, E McKiernan, JP Mehta, E Ryan, P Gammell, H Joyce, N O'Donovan, N Walsh, M Clynes. Investigation of the molecular profile of basal cell carcinoma using whole genome microarrays. Mol Cancer 5: 74-82, 2006

L O'Driscoll, M Clynes. Biomarkers and multiple drug resistance in breast cancer. Current Cancer Drug Targets 6: 365-384, 2006

N Walsh, S Kennedy, A Larkin, S Roy, W Ooi, G Gullo, J Ballot, M Clynes, J Crown, L O'Driscoll. MDR1/P-glycoprotein and MRP-1 protein expression in pancreatic (CaP) & non-small cell lung cancers (NSCLC). Ann. Oncol 17: ix64-ix65, 2006

L O'Driscoll, P Doolan, M Clynes. Novel Panel of Diagnostic, Prognostic & Predictive Biomarkers & Potential Therapeutic Targets for Breast Cancer (filed 26 th April 2007) IE2007/0308

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