Epigenetic modulating compounds as potential adjunct therapeutic agents for treatment of drug-resistant oesophageal squamous cell carcinoma

Dr Órla P Barry & Dr Sharon McKenna

Oesophageal cancer is an aggressive cancer that is poorly studied. The clinical challenge with oesophageal cancer is limited efficacy with current anti-cancer drug regimens resulting in both local and metastatic recurrence. Traditional cytotoxic drugs (cisplatin & 5-fluorouracil) remain the treatment of choice, however, they have little effect on overall survival rates.  Thus, new strategies are necessary to improve treatment options for patients with oesophageal cancer.

Recent genome and whole exome sequencing have identified widespread epigenetic dysregulation in oesophageal cancer. Epigenetics is a relatively new field of molecular biology. It is a complex mechanism of gene regulation, defined as the collection of heritable changes in DNA that affect the packaging of chromatin. Epigenetic changes are different from mutations that change the underlying structure of DNA and have a normal and vital process in cell differentiation and development. In general, however, cancer (including oesophageal cancer) is a disease of widespread epigenetic dysregulation that interacts extensively with underlying genetic mutations. Epigenetic changes are reversible and thus can be manipulated pharmacologically.

Presently, the team is investigating whether epigenetic modifiers can chemo sensitise oesophageal cancer cells to conventional chemotherapeutic drugs. Roisin will focus particularly on oesophageal cancers that currently do not respond well to anticancer drugs. It is her and the team’s desire that epigenetic therapy may be identified as an efficacious adjuvant treatment strategy for patients with oesophageal cancer.

Research Findings

Publications

Cassidy RM, McKenna SL, Barry OP. Evaluation of Cytotoxic Activity of Epigenetic Drugs in Oesophageal Squamous Cell Carcinoma. European Journal of Medical and Health Sciences. 2023; 5(2): 25-36. https://www.ejmed.org/index.php/ejmed/article/view/1618/988