Decitabine, a new star in epigenetic therapy: the clinical application and biological mechanism in solid tumors

Epigenetic alterations are strongly associated with cancer development and drug resistance. The use of the DNA methylation inhibitor decitabine (Dacogen (R)) has been approved in the treatment of hematological malignancies, and its clinical effects on solid tumors have gained attention. Here, we present a review of the molecular regulation mechanisms, clinical experiences and biological evaluation for novel decitabine-based therapies in solid tumors. We also discuss the following questions: What is the best administration schedule of decitabine in solid tumors? Is there tumor type specificity for decitabine-based epigenetic therapy? What are the biological function and mechanism of decitabine in suppressing tumor development? Is there a correlation between DNA demethylation and clinical response? Importantly, low-dose decitabine and combined therapy show significant improvement in solid tumor treatment. However, the correlation studies are preliminary, and key biomarkers for prognosis need further investigation. (C) 2014 Elsevier Ireland Ltd. All rights reserved.