<scp>PARP</scp> mediated <scp>DNA</scp> damage response, genomic stability and immune responses

Zong, Chunyan; Zhu, Tianyu; He, Jie; Huang, Rui; Jia, Renbing; Shen, Jianfeng

doi:10.1002/ijc.33918

Cited by 29 publications

(34 citation statements)

References 191 publications

(355 reference statements)

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“…The expression of NKG2DL in tumor cells may be the result of cGAS/STING pathway-induced IFN-1 expression (Fig. 2 ) [ 115 ].…”

Section: The Mechanism Of Altered Ddr Pathway Affecting the Efficacy ...mentioning

confidence: 99%

“…More importantly, the benefits of DDR inhibitors have been extended to other immunotherapies beyond ICB [ 130 ]. Although the role of the DDR pathway dysfunction in tumor progression and immune regulation is somewhat uncertain [ 58 , 112 , 251 ] and not always useful [ 58 , 83 , 110 , 115 , 181 ].…”

Section: Prospectsmentioning

confidence: 99%

“…This may entail devising novel strategies that dynamically detect DNA repair function and essentially avoid the associated errors caused by the time heterogeneity of somatic mutations [ 58 ]. (2) It is necessary to determine reliable predictive biomarkers, pay more attention to the prediction results of the DDR pathway co-mutation, and determine the appropriate unified labeling threshold [ 87 , 115 ]. (3) Emphasis should be placed on investigative efforts aimed at defining the predictive role of the overall activation level of the DDR pathway.…”

Section: Prospectsmentioning

confidence: 99%

“…For example, ATM inhibitors are used in ATM defective tumors with positive effect [ 252 ]. Meanwhile, drug selection, dosage, and combination time are all carefully considered during personalized treatment, in addition to toxicity, immune-related adverse events, and drug resistance [ 112 , 115 ]. Tumor type should also be considered in combination therapy.…”

Section: Prospectsmentioning

confidence: 99%

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The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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As our understanding of the mechanisms of cancer treatment has increased, a growing number of studies demonstrate pathways through which DNA damage repair (DDR) affects the immune system. At the same time, the varied response of patients to immune checkpoint blockade (ICB) therapy has prompted the discovery of various predictive biomarkers and the study of combination therapy. Here, our investigation explores the interactions involved in combination therapy, accompanied by a review that summarizes currently identified and promising predictors of response to immune checkpoint inhibitors (ICIs) that are useful for classifying oncology patients. In addition, this work, which discusses immunogenicity and several components of the tumor immune microenvironment, serves to illustrate the mechanism by which higher response rates and improved efficacy of DDR inhibitors (DDRi) in combination with ICIs are achieved.

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“…The expression of NKG2DL in tumor cells may be the result of cGAS/STING pathway-induced IFN-1 expression (Fig. 2 ) [ 115 ].…”

Section: The Mechanism Of Altered Ddr Pathway Affecting the Efficacy ...mentioning

confidence: 99%

Section: Prospectsmentioning

confidence: 99%

Section: Prospectsmentioning

confidence: 99%

Section: Prospectsmentioning

confidence: 99%

See 2 more Smart Citations

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

Shi

Qin

Lin

et al. 2022

J Exp Clin Cancer Res

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“…However, HR generally starts in the G2/S period, and the mechanism of HR is more complicated than that of NHEJ [ 8 ]. Poly (ADP-ribose) polymerase1 (PARP1) act as a multifunctional enzyme to catalyze many DNA repair factors involved in DNA repair process to maintain genome stability [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

LINC01419 Promotes the Proliferation of Hepatoma Cells by Recruiting XRCC5 and Regulating Its Phosphorylation to Repair DNA Damage

Liu

Zhang

et al. 2022

Disease Markers

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Background. Hepatocellular carcinoma (HCC) is one of the most common and fatal malignancies in human beings. Studies have shown that long non-coding RNAs (lncRNAs) play key parts in the occurrence and development of HCC. Although many lncRNAs have been studied in the HCC specifically for DNA damage repair, the role of LINC01419 in cellular DNA damage repair has not yet been studied. Objective. This study is aimed at exploring the biological role of LINC01419 and its potential mechanism in HCC. Methods. qRT-PCR was used to detect the expression level of LINC01419 in HCC tissues and cells, the proteins which were involved were detected by Western blot. Effect of LINC01419 knockdown on cell cycle, apoptosis, DNA damage, cell proliferation, wound healing, colony formation, and migration of HCC cells was studied in vitro. Results. The analysis showed that LINC01419 was overexpressed in HCC tissues and cells. Silencing of LINC01419 expression significantly inhibited the proliferation and migration ability of the HCC cells and resulted in cell cycle arrest at G0/G1 phase. Furthermore, the knockdown of LINC01419 increased the DNA damage, and to some extent, promoted sensitivity of HCC cells to doxorubicin. In addition, we performed RIP analysis which showed XRCC5 as a potential protein related to DNA damage repair in hepatoma cells. Conclusion. In conclusion, the LINC01419 acts as an oncogene in HCC and regulates DNA damage repair through XRCC5 in HCC cells.

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A Molecular‐Targeting Photosensitizer to Inhibit DNA Damage Repair System and Induce cGAS‐STING Pathway Activation for Photo‐Immunotherapy of Ovarian Cancer

Fan,

Zhang,

Gan

et al. 2024

Adv Funct Materials

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Poly(ADP‐ribose) polymerase (PARP) inhibitors are commonly utilized in the clinical management of patients with platinum‐sensitive recurrent and late‐stage ovarian cancer, which constitutes a significant proportion of gynecological cancer‐related mortality. Nonetheless, the constraints of their monofunctional properties and limited therapeutic efficacy observed in advanced cancer cases necessitate the exploration of more potent therapeutic strategies for the management of ovarian cancer. The present study describes the development of QTABI, a PARP‐targeting photosensitizer capable of producing reactive oxygen species with light irradiation. Simultaneously, it exhibits significant inhibition of PARP activity, induction of deoxyribonucleic acid (DNA) damage, and consequent synthetic lethality. Furthermore, QTABI can effectively promote the accumulation of cytosolic DNA and activate the cyclicGMP‐AMP synthase (cGAS)‐stimulator of interferon gene (STING) pathway under light irradiation, thereby eliciting potent anti‐tumor immune responses and ultimately boosting anti‐cancer efficacy. Collectively, these findings suggest that QTABI is a multi‐functional photosensitizer, which targets the DNA‐damaging repair system and activates the cGAS‐STING pathway, offering a promising combination photo‐immunotherapy strategy for treating ovarian cancer.

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PARP mediated DNA damage response, genomic stability and immune responses

Cited by 29 publications

References 191 publications

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

The role of DNA damage repair (DDR) system in response to immune checkpoint inhibitor (ICI) therapy

LINC01419 Promotes the Proliferation of Hepatoma Cells by Recruiting XRCC5 and Regulating Its Phosphorylation to Repair DNA Damage

A Molecular‐Targeting Photosensitizer to Inhibit DNA Damage Repair System and Induce cGAS‐STING Pathway Activation for Photo‐Immunotherapy of Ovarian Cancer

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