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• genetics, genomics and molecular biology
• infectious disease and the immune system
• cancer/oncology

• Medicine
• Surgery
• Obstetrics and Gynaecology
• Pathology

• Endocrinology
• Gastroenterology
• Immunology
• Oncology
• Pharmacology

The Molecular Oncology Laboratory at the Dept. of Molecular & Cellular Therapeutics is a vibrant, well funded and dynamic research group with extensive experience in the discovery of molecular determinants of cancer progression (via transcriptomic/proteomic/genomic profiling and functional genomic screening) and their clinical translation through the development and analysis of tissue microarrays, in addition to functional analysis using in vitro models and xenograft studies utilising small animal imaging approaches. As such, we have established an integrated workflow for the molecular and clinical analysis of central tumourigenic processes that we are currently applying to a number of different tumour types, with a strong emphasis on breast and colon cancer.

The lab is part of the Irish Cancer Society-funded Breast-Predict cancer centre (www.breastpredict.com) and has participated in major international research programmes such as the FP7 RATHER (www.ratherproject.com) and Angiopredict (www.angiopredict.com) consortia. Funded by Science Foundation Ireland and the Irish Cancer Society, our current focus is on the development of novel decision support tools for clinicians and the characterisation of dynamic changes that occur in tumours during therapy, including the role of infiltrating lymphocytes in determining response to treatment.

Recent reports from the neoALLTO and TRYPHAENA trials suggest that the pre- and post-treatment immune milieu is fundamental to determining response to dual blockade of the Her2 receptor in breast cancer. TCHL (ICORG 10-05, NCT01485926) is a completed phase II NeoAdjuvant study of women with Her2+ Breast cancer who were randomly assigned two different regimens to assess the impact on pathological Complete Response (pCR) of docetaxel/carboplatin chemotherapy plus tratsuzumab (TCH) versus docetaxel/carboplatin chemotherapy plus tratsuzumab and lapatinib (TCHL). As such, it represents an ideal study to compare two different Her2-targeted regimens in a prospectively collected and randomized cohort. Eighty-eight patients were enrolled on the trial and samples were longitudinally collected for future analysis. Fresh-Frozen (FF) samples from patients both pre-treatment and after 1 round of therapy (21 days post-treatment) were collected, in addition to baseline serum, plasma and peripheral blood mononuclear cell fractions. Blood samples were also collected during routine follow-up throughout treatment, as well as surgical resections of residual tumor following treatment and biopsies of any tumor recurrences.

We aim to characterise the nature of the immune infiltrate in these longitudinally collected samples using multiplexed fluorescent immunohistochemistry and advanced image analysis solutions to determine the role the adaptive immune response plays in modulating therapeutic efficacy. Next generation seqeuncing of tumour samples will also be performed and in silico deconvolution of leukocyte populations used to define the lymphocytic infiltrate phenotype. Preliminary data suggests activation of immune checkpoints in poor responders, as such we also aim to determine whether such patients would be candidates for immunotherapy. Considerable support for the project is already in place (bioinformatics/systems biology postdoc and 2 molecular Biology PhDs directly supported by SFI for this programme), as such, the candidate would be joining an existing and well functioning multidisciplinary team.