Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jun 15, 2021; 13(6): 574-588
Published online Jun 15, 2021. doi: 10.4251/wjgo.v13.i6.574
Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment
Keun-Yeong Jeong, Minhee Park
Keun-Yeong Jeong, Minhee Park, Research and Development, Metimedi Pharmaceuticals, Incheon 22006, South Korea
Author contributions: Jeong KY collected references and designed the contents; Jeong KY and Park MH wrote the manuscript; all authors have read and approved the final manuscript.
Conflict-of-interest statement: We have no conflict of interest to declare.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Corresponding author: Keun-Yeong Jeong, PhD, Executive Vice President, Research Assistant Professor, Research and Development, Metimedi Pharmaceuticals, 263 Central-ro, Incheon 22006, South Korea.
Received: February 25, 2021
Peer-review started: February 25, 2021
First decision: April 19, 2021
Revised: April 22, 2021
Accepted: May 8, 2021
Article in press: May 8, 2021
Published online: June 15, 2021

The development of colorectal cancer (CRC) can result from changes in a variety of cellular systems within the tumor microenvironment. Particularly, it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC progression. Based on this background, the potential to focus on poly [adenosine diphosphate (ADP)-ribose] polymerase (PARP)-1 and poly-ADP ribosylation (PARylation) as the main causes of malignant formation of CRC may be considered. One of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid (DNA) repair function, which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and superoxide. PARP-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin enzymes. Given the high importance of these processes in CRC, it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC progression. Therefore, this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles; furthermore, it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting CRC. This understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC, which may present the potential to identify various research topics that can be challenged both non-clinically and clinically.

Keywords: Colorectal cancer, Poly adenosine diphosphate-ribose polymerase-1, Poly adenosine diphosphate-ribose, Poly-adenosine diphosphate ribosylation

Core Tip: The main focus is on highlighting the pivotal role of poly adenosine diphosphate-ribose polymerase-1 (PARP-1) and poly-adenosine diphosphate ribosylation (PARylation) in regulating deoxyribonucleic acid damage response, redox homeostasis, chromosomal instability, and transcriptional activity under the common denominator of overcoming the genomic instability in colorectal cancer (CRC). The importance of targeting PARP-1 and PARylation in the treatment of CRC will be emphasized because the level of understanding of pathological changes leading to malignant transformation of CRC by PARP-1 and PARylation may increase.