1022 – TARGETING THE EPIGENOME IN CANCER

Abstract

A hallmark of haematological malignancies, particularly acute myeloid leukaemia (AML) is epigenetic dysregulation, which is initiated by recurrent translocations and/or mutations in transcription factors and chromatin regulators. This manifests as a block in myeloid differentiation and an increase in malignant self-renewal. These common features of AML have led to widespread optimism that epigenetic therapies would dramatically change the natural history of this disease. Whilst pre-clinical studies with these drugs fuelled this optimism, results from early clinical trials have offered a more sobering message. The challenge that lies ahead is understanding the molecular mechanisms that govern sensitivity and resistance to these agents. These insights will in turn guide the rational use of these exciting new drugs in the clinical arena. In this session, I will focus on the molecular and cellular mechanisms of action of some of these drugs and the pre-clinical evidence for their efficacy. I will particularly highlight new epigenetic therapies that recently been developed. I will also discuss the emerging evidence for how epigenetic regulators may influence the development of therapeutic resistance to conventional and targeted therapies and highlight potential new strategies that may forestall or circumvent therapeutic resistance.