Open AccessPoly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment
Author(s) -
KeunYeong Jeong,
Min Hee Park
Publication year - 2021
Publication title -
world journal of gastrointestinal oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.924
H-Index - 26
ISSN - 1948-5204
DOI - 10.4251/wjgo.v13.i6.574
Subject(s) - epigenetics , chromatin remodeling , histone , cancer research , chromatin , dna repair , poly adp ribose polymerase , synthetic lethality , genome instability , colorectal cancer , dna damage , pi3k/akt/mtor pathway , medicine , cancer , parp inhibitor , biology , microbiology and biotechnology , genetics , gene , polymerase , dna , signal transduction
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.