Novel epigenetic therapies in hematological malignancies: Current status and beyond


Type
Article
Change log
Authors
Huntly, BJP 
Abstract

Over the last decade transcriptional dysregulation and altered epigenetic programs have emerged as a hallmark in the majority of hematological cancers. Several epigenetic regulators are recurrently mutated in many hematological malignancies. In addition, in those cases that lack epigenetic mutations, altered function of epigenetic regulators has been shown to play a central role in the pathobiology of many hematological neoplasms, through mechanisms that are becoming increasingly understood. This, in turn, has led to the development of small molecule inhibitors of dysregulated epigenetic pathways as novel targeted therapies for hematological malignancies. In this review, we will present the most recent advances in our understanding of the role played by dysregulated epigenetic programs in the development and maintenance of hematological neoplasms. We will describe novel therapeutics targeting altered epigenetic programs and outline their mode of action. We will then discuss their use in specific conditions, identify potential limitations and putative toxicities while also providing an update on their current clinical development. Finally, we will highlight the opportunities presented by epigenetically targeted therapies in hematological malignancies and introduce the challenges that need to be tackled by both the research and clinical communities to best translate these novel therapies into clinical practice and to improve patient outcomes.

Description
Keywords
hematological malignancies, epigenetics, targeted therapy
Journal Title
Seminars in Cancer Biology
Conference Name
Journal ISSN
1044-579X
1096-3650
Volume Title
Publisher
Elsevier
Sponsorship
Wellcome Trust (109967/Z/15/Z)
Medical Research Council (MC_PC_12009)
Medical Research Council (MR/M010392/1)
Worldwide Cancer Research (None)
We would like to thank all the members of the Huntly laboratory and our funders including the European Research Council, MRC, Bloodwise, the Kay Kendall Leukaemia Fund, the Wellcome Trust, the Cambridge NIHR Biomedical Research Centre, and core support grants to the Wellcome Trust - Medical Research Council Cambridge Stem Cell Institute.