Editorial
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2021; 13(11): 1544-1550
Published online Nov 15, 2021. doi: 10.4251/wjgo.v13.i11.1544
Inhibition of poly (ADP-Ribose) polymerase: A promising strategy targeting pancreatic cancer with BRCAness phenotype
Keun-Yeong Jeong, Haejun Lee
Keun-Yeong Jeong, R&D Center, Metimedi Pharmaceuticals, Incheon 22006, South Korea
Haejun Lee, Department of Nuclear Medicine, Gil Medical Center, Incheon 21565, South Korea
Author contributions: Jeong KY conceived the contents and drafted the manuscript; Jeong KY and Lee H revised the manuscript; and all authors approved the final version of the article.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Keun-Yeong Jeong, PhD, Executive Vice President, Research Assistant Professor, R&D Center, Metimedi Pharmaceuticals, 263 Central ro, Incheon 22006, South Korea. alvirus@naver.com
Received: March 17, 2021
Peer-review started: March 17, 2021
First decision: April 19, 2021
Revised: April 20, 2021
Accepted: September 10, 2021
Article in press: September 10, 2021
Published online: November 15, 2021
Abstract

The use of chemotherapeutic regimens for the treatment of pancreatic cancer is still limited because pancreatic cancer is usually diagnosed at an advanced stage as a refractory disease in which symptoms are difficult to recognize in the early stages. Furthermore, at advanced stages, there are important challenges to achieve clinical benefit and symptom resolution, even with the use of an expanded spectrum of anticancer drugs. Recently, a point of reduced susceptibility to conventional chemotherapies by breast cancer susceptibility gene (BRCA) mutations led to a new perspective for overcoming the resistance of pancreatic cancer within the framework of increased genome instability. Poly (ADP-Ribose) polymerase (PARP) -1 is an enzyme that can regulate intrinsic functions, such as response to DNA damage. Therefore, in an environment where germline mutations in BRCAs (BRCAness) inhibit homologous recombination in DNA damage, resulting in a lack of DNA damage response, a key role of PARP-1 for the adaptation of the genome instability could be further emphasized. Here, we summarized the key functional role of PARP-1 in genomic instability of pancreatic cancer with the BRCAness phenotype and listed clinical applications and outcomes of PARP-1 inhibitors to highlight the importance of targeting PARP-1 activity.

Keywords: Pancreatic cancer, BRCAness, Poly (ADP-Ribose) polymerase-1, PARylation, Poly (ADP-Ribose) polymerase-1 inhibitor

Core Tip: The incidence of germline mutations of the breast cancer susceptibility gene (BRCA), defined as BRCAness, that can be targeted for pancreatic cancer is 9%-17%. Mutations in BRCAs are responsible for causing genetic instability and worsening the prognosis. Therefore, inhibition of poly (ADP-Ribose) polymerase-1 has emerged as a promising therapeutic target for BRCAness pancreatic cancer within the framework of an increase in genome instability.