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• cancer/oncology
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Cell Biology, Autophagy, Predictive Biomarkers

• Medicine
• Pathology

• Oncology
• Other

pathology

The Autophagy in Cancer Group is based in Cancer Research @UCC – a dedicated research Centre established to promote translational research in Cancer. This research team are investigating how the cellular process of autophagy can influence advanced cancer biology. Constitutive autophagy is an important homeostatic process, which responds to metabolic demand and acts as a quality control process by removing superfluous cellular material and damaged organelles. It can therefore be protective against cancer. However, in established cancers, autophagy takes on new roles and helps cancer cells to survive in growth limiting conditions and can help them to resist various types of therapy. Recent research in this group has been evaluating how autophagy biomarkers can predict response to chemotherapy and overall patient outcome (S El-Mashed et al., Apoptosis and autophagy markers predict survival in oesophageal adenocarcinoma. In Press. BMC Cancer 2022 and PMID 26265176), identification of novel molecular targets that can regulate autophagy (PMID:28186990) and evaluation of novel treatment regimens to improve efficacy and overall outcome for cancer patients (PMID:26248051, A Phase Ib Trial, EUDRACT: 2014-000186-47).

Our group has a particular interest in oesophageal cancer which is a poor prognosis cancer with European 1-year and 5-year survival rates of 40 % and 12 % respectively, (2015 EUROCARE-5 study). Late presentation and resistance to therapy are major limitations. Novel biomarkers and new therapeutic targets are urgently required. We have been examining patient tissue for a bio-marker of autophagy (LC3) and have correlated expression with clinical features and overall survival. We now want to examine further makers involved in the regulation of autophagy and examine at a cell biology level the function of biomarkers associated with clinical outcome.
We have also been investigating the death and survival programs initiated in oesophageal cancer cells in response to chemotherapeutic agents. We have panels of cell lines that respond in different ways to therapeutic agents. One panel will respond with both apoptosis and autophagy and is relatively drug sensitive whereas more resistant cells fail to induce apoptosis and respond by undergoing autophagy only with limited Type II cell death. Differential expression of an interferon-related gene signature was associated with these phenotypes and confirmed at the protein level. A related gene signature has also been previously reported as a novel biomarker of sensitivity in other cancers (PMID:1900127; PMID:18566215; (PMID:29296177). We have already demonstrated an impact on autophagy of some of these genes in expressing cells (PMID:28186990), which we want to explore further. We will also explore whether any of these genes represent useful clinical biomarkers in oesophageal cancer.
We would like a Trainee to become an integral part of this overall team effort and we are particularly interested in those with pathology expertise to investigate biomarkers in oesophageal cancer tissue. A medical oncology background would also be suitable for projects looking at the impact of autophagy on chemoresistance.

I have previously supervised 9 PhD’s to completion. Three of these were Clinical trainees and six are scientists. Potential joint supervisors for this program include:

Dr. Cynthia Heffron, Clinical Senior Lecturer and Consultant Histopathologist, Cork University Hospital, Wilton, Cork.

Dr. Derek Power, Clinical Senior Lecturer and Consultant Medical Oncologist, Cork University Hospital, Wilton, Cork.