Recent developments in epigenetic cancer therapeutics: clinical advancement and emerging trends
Top Cited Papers
Open Access
- 12 April 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Biomedical Science
- Vol. 28 (1), 1-58
- https://doi.org/10.1186/s12929-021-00721-x
Abstract
Epigenetic drug discovery field has evidenced significant advancement in the recent times. A plethora of small molecule inhibitors have progressed to clinical stage investigations and are being explored exhaustively to ascertain conclusive benefits in diverse malignancies. Literature precedents indicates that substantial amount of efforts were directed towards the use of epigenetic tools in monotherapy as well as in combination regimens at the clinical level, however, the preclinical/preliminary explorations were inclined towards the identification of prudent approaches that can leverage the anticancer potential of small molecule epigenetic inhibitors as single agents only. This review article presents an update of FDA approved epigenetic drugs along with the epigenetic inhibitors undergoing clinical stage investigations in different cancer types. A detailed discussion of the pragmatic strategies that are expected to steer the progress of the epigenetic therapy through the implementation of emerging approaches such as PROTACS and CRISPR/Cas9 along with logical ways for scaffold fabrication to selectively approach the enzyme isoforms in pursuit of garnering amplified antitumor effects has been covered. In addition, the compilation also presents the rational strategies for the construction of multi-targeting scaffold assemblages employing previously identified pharmacophores as potential alternatives to the combination therapy.Keywords
Funding Information
- Ministry of Science and Technology, Taiwan (109-2113-M-038 -001, 108-2320-B-038-010-MY2)
This publication has 316 references indexed in Scilit:
- Mechanisms and Functions of ATP-Dependent Chromatin-Remodeling EnzymesCell, 2013
- The Histone Demethylase KDM1A Sustains the Oncogenic Potential of MLL-AF9 Leukemia Stem CellsCancer Cell, 2012
- Increased EID1 nuclear translocation impairs synaptic plasticity and memory function associated with pathogenesis of Alzheimer's diseaseNeurobiology of Disease, 2012
- Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain FamilyCell, 2012
- Disulfiram is a DNA demethylating agent and inhibits prostate cancer cell growthThe Prostate, 2010
- Rational Design and Simple Chemistry Yield a Superior, Neuroprotective HDAC6 Inhibitor, Tubastatin AJournal of the American Chemical Society, 2010
- Histone deacetylase inhibitors: Potential in cancer therapyJournal of Cellular Biochemistry, 2009
- EZH1 Mediates Methylation on Histone H3 Lysine 27 and Complements EZH2 in Maintaining Stem Cell Identity and Executing PluripotencyMolecular Cell, 2008
- Histone Demethylation Mediated by the Nuclear Amine Oxidase Homolog LSD1Cell, 2004
- Upregulation and Nuclear Recruitment of HDAC1 in Hormone Refractory Prostate CancerThe Prostate, 2004