Poly adenosine diphosphate-ribosylation, a promising target for colorectal cancer treatment

Abstract

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.