Epigenetic modulating compounds as potential adjunct therapeutic agents for treatment of drug-resistant oesophageal squamous cell carcinoma
Oesophageal cancer is an aggressive cancer which 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 has 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 on DNA that affects the packaging of chromatin. Epigenetic changes are different from mutations that change the underlying structure of DNA and has 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 are investigating whether epigenetic modifiers can chemosensitise oesophageal cancer cells to conventional chemotherapeutic drugs. Roisin will focus particularly on oesophageal cancers that currently does not respond well to anticancer drugs. It is hers and the teams desire that epigenetic therapy may be identified as an efficacious adjuvant treatment strategy for patients with oesophageal cancer.Back