Promises and challenges of anticancer drugs that target the epigenome

Abstract

The occurrence of epigenetic aberrations in cancer and their role in promoting tumorigenesis has led to the development of various small molecule inhibitors that target epigenetic enzymes. In preclinical settings, many epigenetic inhibitors demonstrate promising activity against a variety of both hematological and solid tumors. The therapeutic efficacy of those inhibitors that have entered the clinic however, is restricted predominantly to hematological malignancies. Here we outline the observed epigenetic aberrations in various types of cancer and the clinical responses to epigenetic drugs. We furthermore discuss strategies to improve the responsiveness of both hematological and solid malignancies to epigenetic drugs.

KEYWORDS::

• cancer
• DNA methylation
• epigenetics
• histone modification
• mouse models
• personalized medicine
• therapeutics

Financial & competing interests disclosure

Supported by the Dutch Cancer Society to Inge Verbrugge (NKI2009-4446) and Michael Bots (AMC2009-4457). Ricky W Johnstone is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, The Victorian Cancer Agency, The Leukemia Foundation of Australia, Victorian Breast Cancer Research Consortium and the Australian Rotary Health Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

Supported by the Dutch Cancer Society to Inge Verbrugge (NKI2009-4446) and Michael Bots (AMC2009-4457). Ricky W Johnstone is a Principal Research Fellow of the National Health and Medical Research Council of Australia (NHMRC) and supported by NHMRC Program and Project Grants, the Susan G Komen Breast Cancer Foundation, the Prostate Cancer Foundation of Australia, Cancer Council Victoria, The Victorian Cancer Agency, The Leukemia Foundation of Australia, Victorian Breast Cancer Research Consortium and the Australian Rotary Health Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.