Professor Tim Maughan

Professor Tim Maughan

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Tim studied medicine at Cambridge and UCH, London and undertook his research training at Cambridge under Prof Norman Bleehen at the MRC Clinical Oncology and Radiotherapeutics Unit.

Thereafter he worked as an NHS consultant Clinical Oncologist in Cardiff, becoming Professor of Cancer Studies in 2007. During that time, he established the first clinical research network, the Wales Cancer Trials Network, and was subsequently involved in the development of the clinical research networks across the UK.

Tim’s research has focused on colorectal cancer: he leads the FOCUS4 trial of molecular selection of treatment with Richard Wilson from Belfast, which is now recruiting patients across the UK. At Paddy’s suggestion he also led the bid for the first MRC stratified medicine consortium in cancer which is jointly led between Oxford and Belfast.

From 2008-10, Professor Maughan was the founding chair of the NCRI Clinical and Translational Radiotherapy Research Working Group (CTRad), which has a broad remit to enhance radiotherapy research in the UK. Professor Maughan was appointed Professor of Clinical Oncology and Deputy Director of the MRC-CRUK Oxford Institute of Radiation Oncology, Department of Oncology at the University of Oxford in 2011.

THE CHALLENGE AND THE PROMISE OF PRECISION MEDICINE IN CANCER
Tim Maughan

Precision medicine by its very name makes a promise of treatment which is precisely tailored for the individual. This has proved an elusive goal in cancer which by its very nature not only varies from person to person but is also evolving in time and place within the individual.

Targeted therapeutics have delivered a few notable advances, but overall the field has seen short-lived responses and a lack of long term disease control. Major clinical trial programmes have been able to allocate less than 20% of patients to ‘targeted therapies’ on the basis of the patient’s tumour genetics. Our efforts in colorectal cancer reveal a complex co-evolution of the tumour and its micro-environment, with critical cross talk between the malignant epithelium, the stroma and the immune response. We have shown that this interaction appears to determine the response to standard chemoradiation in rectal cancer, through TGF signalling and immune exclusion. The cytokine IL-23 pathway drives poor prognosis in KRAS mutant CRC. Stromal derived Gremlin signalling drives tumourigenesis.

This tumour microenvironment cross talk is not revealed by analysis of genetic sequence but by transcriptional profiles reflecting the altered biological behaviour of stroma, epithelial and immune elements. This insight drives us to focus on detailed analysis of the conversation going on between elements of the tumour microenvironment, how they together behave as a malignant tissue and how that conversation can be manipulated to clinical benefit. This broader paradigm may help in identifying new ways to make progress in challenging malignancies where both targeted therapy and immunotherapy have so far proved unsuccessful.

3D mammosphere culture of breast epithelial cell line MCF10A.

Courtesy of Dr. Emer Bourke, NUI Galway

Phospho-Akt expression and localisation

Mediated by VEGF in A549 lung cancer cells. Visualised by high content image analysis.

Courtesy of Dr Martin Barr, Clinical Scientist & Adjunct Assistant Professor, St James’s Hospital & Trinity College Dublin

Metaphase chromosome spread of Jurkat T-lymphoma cells

Courtesy of Rebecca Gorry, PhD Student, Mc Gee Lab, UCD School of Biomolecular & Biomedical Science, Conway Institute, UCD

Apoptosis assessment of SKMES-1 lung cancer cells

Using a multiparameter apoptosis staining kit, showing cell nuclei (blue), actin (green) and mitochondrial activity (orange).

Courtesy of Dr Martin Barr, Clinical Scientist & Adjunct Assistant Professor, St James’s Hospital & Trinity College Dublin

HeLa Cells

Courtesy of Rebecca Gorry, PhD Student, Mc Gee Lab, UCD School of Biomolecular & Biomedical Science, Conway Institute, UCD

IACR & EACR Joint Conference 2020

26 — 28 February 2020 at Galway Bay Hotel, Galway

Mitotic Chronic Myelogenous Leukaemia K562 Cells

Courtesy of Rebecca Gorry, PhD Student, Mc Gee Lab, UCD School of Biomolecular & Biomedical Science, Conway Institute, UCD

Cell to Cell Tweeting

Via nanoparticles (red) in Triple Negative Breast Cancer (TNBC)

Courtesy of Sinéad Lindsay, UCD Conway Institute of Biomolecular and Biomedical Research, University College Dublin (UCD) Ireland.

Confocal Microscopy Analysis

Of phospho-Akt expression in H460 lung cancer cells in response to hypoxia (0.5% O2).

Courtesy of Dr Martin Barr, Clinical Scientist & Adjunct Assistant Professor, St James’s Hospital & Trinity College Dublin

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