Histone Modifying Enzymes as Targets for Therapeutic Intervention in Oesophageal Adenocarcinoma

SIMPLE SUMMARY: Despite advances in both the surgical and medical management of oesophageal adenocarcinoma (OAC), overall prognosis remains poor, with less than 1 in 5 patients surviving more than 5 years from diagnosis. Patients suitable for treatment with curative intent receive pre-operative chemotherapy, but few (<20%) gain a clinically meaningful response. Epigenetic targets have been identified as key drivers in OAC. With therapies targeting histone-modifying enzymes (HME) already in clinical use in several cancer types, they may be a potential novel therapeutic in OAC. This review outlines the current literature surrounding the roles of HMEs in OAC tumorignesis and therapeutic efficacy. ABSTRACT: Oesophageal adenocarcinoma (OAC) has a dismal prognosis, where curable disease occurs in less than 40% of patients, and many of those with incurable disease survive for less than a year from diagnosis. Despite the widespread use of systematic chemotherapy in OAC treatment, many patients receive no benefit. New treatments are urgently needed for OAC patients. There is an emerging interest in epigenetic regulators in cancer pathogenesis, which are now translating into novel cancer therapeutic strategies. Histone-modifying enzymes (HMEs) are key epigenetic regulators responsible for dynamic covalent histone modifications that play roles in both normal and dysregulated cellular processes including tumorigenesis. Several HME inhibitors are in clinical use for haematological malignancies and sarcomas, with numerous on-going clinical trials for their use in solid tumours. This review discusses the current literature surrounding HMEs in OAC pathogenesis and their potential use in targeted therapies for this disease.