PARP inhibitors in gastric cancer: beacon of hope
Open Access
- 24 June 2021
- journal article
- review article
- Published by Springer Science and Business Media LLC in Journal of Experimental & Clinical Cancer Research
- Vol. 40 (1), 1-13
- https://doi.org/10.1186/s13046-021-02005-6
Abstract
Defects in the DNA damage response (DDR) can lead to genome instability, producing mutations or aberrations that promote the development and progression of cancer. But it also confers such cells vulnerable to cell death when they inhibit DNA damage repair. Poly (ADP-ribose) polymerase (PARP) plays a central role in many cellular processes, including DNA repair, replication, and transcription. PARP induces the occurrence of poly (ADP-ribosylation) (PARylation) when DNA single strand breaks (SSB) occur. PARP and various proteins can interact directly or indirectly through PARylation to regulate DNA repair. Inhibitors that directly target PARP have been found to block the SSB repair pathway, triggering homologous recombination deficiency (HRD) cancers to form synthetic lethal concepts that represent an anticancer strategy. It has therefore been investigated in many cancer types for more effective anti-cancer strategies, including gastric cancer (GC). This review describes the antitumor mechanisms of PARP inhibitors (PARPis), and the preclinical and clinical progress of PARPis as monotherapy and combination therapy in GC.Keywords
Funding Information
- the Colorectal Cancer Medical Seeds Research Fund (2019095)
This publication has 110 references indexed in Scilit:
- On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1Genes & Development, 2012
- ADP-ribose polymers localized on Ctcf–Parp1–Dnmt1 complex prevent methylation of Ctcf target sitesBiochemical Journal, 2011
- Poly (ADP-ribose) polymerase (PARP) is not involved in base excision repair but PARP inhibition traps a single-strand intermediateNucleic Acids Research, 2010
- PARP inhibition: PARP1 and beyondNature Reviews Cancer, 2010
- The DNA-damage response in human biology and diseaseNature, 2009
- Early steps in the DNA base excision/single-strand interruption repair pathway in mammalian cellsCell Research, 2008
- Poly(ADP-ribose)polymerase inhibition decreases angiogenesisBiochemical and Biophysical Research Communications, 2006
- PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathwaysNucleic Acids Research, 2006
- The Concept of Synthetic Lethality in the Context of Anticancer TherapyNature Reviews Cancer, 2005
- The PARP superfamilyBioEssays, 2004