The role of DNA-demethylating agents in cancer therapy

DNA methylation patterns are frequently altered in cancer cells as compared to normal cells. A large body of research associates these DNA methylation aberrations with cancer initiation and progression. Moreover, cancer cells seem to depend upon these aberrant DNA methylation profiles to thrive. Finally, DNA methylation modifications are reversible, highlighting the potential to target the global methylation patterns for cancer therapy. In this review, we will discuss the scientific and clinical aspects of DNA methylation in cancer. We will review the limited success of targeting DNA methylation in the clinic, the associated clinical challenges, the impact of novel DNA methylation inhibitors and how combination therapies are improving patient outcomes. (C) 2019 Elsevier Inc. All rights reserved.