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Current Cancer Drug Targets


ISSN (Print): 1568-0096
ISSN (Online): 1873-5576

Review Article

PROTACs: Promising Approaches for Epigenetic Strategies to Overcome Drug Resistance

Author(s): Sarah F. Giardina*, Elena Valdambrini, J. David Warren and Francis Barany

Volume 21, Issue 4, 2021

Published on: 02 February, 2021

Page: [306 - 325] Pages: 20

DOI: 10.2174/1568009621666210203110857

Price: $65


Epigenetic modulation of gene expression is essential for tissue-specific development and maintenance in mammalian cells. Disruption of epigenetic processes, and the subsequent alteration of gene functions, can result in inappropriate activation or inhibition of various cellular signaling pathways, leading to cancer. Recent advancements in the understanding of the role of epigenetics in cancer initiation and progression have uncovered functions for DNA methylation, histone modifications, nucleosome positioning, and non-coding RNAs. Epigenetic therapies have shown some promise for hematological malignancies, and a wide range of epigenetic-based drugs are undergoing clinical trials. However, in a dynamic survival strategy, cancer cells exploit their heterogeneous population which frequently results in the rapid acquisition of therapy resistance. Here, we describe novel approaches in drug discovery targeting the epigenome, highlighting recent advances the selective degradation of target proteins using Proteolysis Targeting Chimera (PROTAC) to address drug resistance.

Keywords: Cancer, oncology, PROTAC, epigenetics, drug resistance, therapy resistance.

Graphical Abstract
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