PARP inhibitors in gastric cancer: beacon of hope

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.

RETRACTED ARTICLE: Long non-coding RNA CCL2 promoted gastric cancer function via miR-128/ PARP2 signal pathway

“…Amounts of studies have previously been uncovered the importance of miRNAs in regulating the development of gastric cancer [ 25–27 ]. Such as miR-331 could inhibited gastric cancer development by targeting MSI1 and it could be used as a predictor and prognostic indicator of gastric cancer [ 28 ].…”

“…Given the important role of lncRNAs, especially CCL2 in cancer, we postulated that it also promotes the oncogenic function of gastric cancer cells. As both miR-128 and PARP2 play critical roles in gastric cancer [ 24 , 25 ], we hypothesized that CCL2 could sponge miR-128, thereby potentially regulating PARP2. The purpose of this study was to explore the mechanism of miR-128/PARP2 signaling pathway mediated by lncRNA CCL2 in gastric cancer, and to propose a novel perspective for gastric cancer treatment.…”

Molecular Targets for Gastric Cancer Treatment and Future Perspectives from a Clinical and Translational Point of View

“…In general, how to best identify HDR is still a very important research area for predicting the efficacy of PARP inhibitors beyond BRCA testing. Furthermore, combinations of PARP inhibitors with immune checkpoint blockade, small molecule inhibitors or antiangiogenic compounds are under way [133] and initial results are promising [134].…”

PARP Inhibitors Display Differential Efficacy in Models of BRCA Mutant High-Grade Serous Ovarian Cancer

“…BRCA1 methylated tumours are also sensitive to PARP inhibition [8], as are tumours with mutations in other genes that function in repair of double strand breaks (DSBs), including RAD51C, RAD51D, ATM and PALB2, where tumours are described as having a "BRCAness" phenotype [8][9][10]. With this broadening concept of BRCAness, other malignancies are being investigated to assess sensitivity to PARP inhibitors, including colorectal, upper gastrointestinal and acute myeloid leukemia [1,[11][12][13].…”