Epigenetic therapy for solid tumors: from bench science to clinical trials

Author:

Juo Yen-Yi1,Gong Xue-Jun23,Mishra Ankita2,Cui Xiao2,Baylin Stephen B4,Azad Nilofer S5,Ahuja Nita254

Affiliation:

1. Department of Surgery, George Washington University Medical Center, 2150 Pennsylvania Ave. NW, Suite 6B, Washington, DC 20037, USA

2. Department of Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA

3. Department of Surgery, Xiangya Hospital of Central South University, Changsha, China

4. Department of Urology Johns Hopkins University School of Medicine, Baltimore, USA

5. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA

Abstract

The cancer epigenome is characterized by global DNA methylation and chromatin changes, such as the hypermethylation of specific CpG island promoters. Epigenetic agents like DNA methyltransferase or histone deacetylase inhibitors induce phenotype changes by reactivation of epigenetically silenced tumor suppressor genes. Despite initial promise in hematologic malignancies, epigenetic agents have not shown significant efficacy as monotherapy against solid tumors. Recent trials showed that epigenetic agents exert favorable modifier effects when combined with chemotherapy, hormonal therapy, or other epigenetic agents. Due to the novel nature of their mechanism, it is important to reconsider the optimal patient selection, drug regimen, study design, and outcome measures when pursuing future trials in order to discover the full potential of this new therapeutic modality.

Publisher

Future Medicine Ltd

Subject

Cancer Research,Genetics

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