The Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer

Burgess, Joshua T.; Rose, Maddison; Boucher, Didier; Plowman, J.; Molloy, Christopher J.; Fisher, Mark A.; O’Leary, Connor; Richard, Derek J.; O’Byrne, Kenneth J.; Bolderson, Emma

doi:10.3389/fonc.2020.01256

Cited by 38 publications

(42 citation statements)

References 166 publications

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“…Reports indicated that during DNA damage BRCA1 co-localizes with phosphorylated H2AFX [21] . Decreased expression of CSB has already been demonstrated to increase the risk of lung cancer [22] . Through Co-Immunoprecipitation the protein-protein interaction of the different proteins involved were seen.…”

Section: Resultsmentioning

confidence: 98%

R-loop modulated epigenetic regulation in T helper cells mechanistically associates coronary artery disease and non-small cell lung cancer

Rakshit

Sunny

George

et al. 2021

Translational Oncology

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Section: Resultsmentioning

confidence: 98%

R-loop modulated epigenetic regulation in T helper cells mechanistically associates coronary artery disease and non-small cell lung cancer

Rakshit

Sunny

George

et al. 2021

Translational Oncology

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“…Although defects in DNA repair lead to large amount of mutations, high mutation load results in high neoantigen load [35] and hence high neoantigen expression may lead to greater immunogenicity. We identified three DNA repair genes, ERCC1, XPA, and XPC, that were negatively correlated with tumor mutation load and neoantigen expression, suggesting that dysregulation of DNA repair pathways may promote genome instability and increase the accumulation of DNA lesions and mutations in tumorigenesis [36]. XPC was negatively associated with the expression of the most shared neoantigens.…”

Section: Discussionmentioning

confidence: 95%

Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival

Amei

Bui

et al. 2021

Cancers

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Neoantigens are derived from tumor-specific somatic mutations. Neoantigen-based synthesized peptides have been under clinical investigation to boost cancer immunotherapy efficacy. The promising results prompt us to further elucidate the effect of neoantigen expression on patient survival in breast cancer. We applied Kaplan–Meier survival and multivariable Cox regression models to evaluate the effect of neoantigen expression and its interaction with T-cell activation on overall survival in a cohort of 729 breast cancer patients. Pearson’s chi-squared tests were used to assess the relationships between neoantigen expression and clinical pathological variables. Spearman correlation analysis was conducted to identify correlations between neoantigen expression, mutation load, and DNA repair gene expression. ERCC1, XPA, and XPC were negatively associated with neoantigen expression, while BLM, BRCA2, MSH2, XRCC2, RAD51, CHEK1, and CHEK2 were positively associated with neoantigen expression. Based on the multivariable Cox proportional hazard model, patients with a high level of neoantigen expression and activated T-cell status showed improved overall survival. Similarly, in the T-cell exhaustion and progesterone receptor (PR) positive subgroups, patients with a high level of neoantigen expression showed prolonged survival. In contrast, there was no significant difference in the T-cell activation and PR negative subgroups. In conclusion, neoantigens may serve as immunogenic agents for immunotherapy in breast cancer.

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“…Additionally, cells will also initiate the DNA damage repair system, which was developed during the evolution of species. There are two major DNA repair pathways: homologous recombination (HR) and non-homologous end joining (NHEJ; Burgess et al, 2020 ; Nastasi et al, 2020 ; Zhao et al, 2020 ).…”

Section: Radiation-induced Cell Response and Mechanism Of Radiotherapmentioning

confidence: 99%

Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

Zhang

Yang

2021

Front. Cell Dev. Biol.

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Head and neck cancers (HNCs) rank as the sixth common and the seventh leading cause of cancer-related death worldwide, with an estimated incidence of 600,000 cases and 40–50% mortality rate every year. Radiotherapy is a common local therapeutic modality for HNC mainly through the function of ionizing radiation, with approximately 60% of patients treated with radiotherapy or chemoradiotherapy. Although radiotherapy is more advanced and widely used in clinical practice, the 5-year overall survival rates of locally advanced HNCs are still less than 40%. HNC cell resistance to radiotherapy remains one of the major challenges to improve the overall survival in HNC patients. Non-coding RNAs (ncRNAs) are newly discovered functional small RNA molecules that are different from messenger RNAs, which can be translated into a protein. Many previous studies have reported the dysregulation and function of ncRNAs in HNC. Importantly, researchers reported that several ncRNAs were also dysregulated in radiotherapy-sensitive or radiotherapy-resistant HNC tissues compared with the normal cancer tissues. They found that ectopically elevating or knocking down expression of some ncRNAs could significantly influence the response of HNC cancer cells to radiotherapy, indicating that ncRNAs could regulate the sensitivity of cancer cells to radiotherapy. The implying mechanism for ncRNAs in regulating radiotherapy sensitivity may be due to its roles on affecting DNA damage sensation, inducing cell cycle arrest, regulating DNA damage repair, modulating cell apoptosis, etc. Additionally, clinical studies reported that in situ ncRNA expression in HNC tissues may predict the response of radiotherapy, and circulating ncRNA from body liquid serves as minimally invasive therapy-responsive and prognostic biomarkers in HNC. In this review, we aimed to summarize the current function and mechanism of ncRNAs in regulating the sensitivity of HNC cancer cells to radiotherapy and comprehensively described the state of the art on the role of ncRNAs in the prognosis prediction, therapy monitoring, and prediction of response to radiotherapy in HNC.

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The Therapeutic Potential of DNA Damage Repair Pathways and Genomic Stability in Lung Cancer

Cited by 38 publications

References 166 publications

R-loop modulated epigenetic regulation in T helper cells mechanistically associates coronary artery disease and non-small cell lung cancer

R-loop modulated epigenetic regulation in T helper cells mechanistically associates coronary artery disease and non-small cell lung cancer

Impact of Neoantigen Expression and T-Cell Activation on Breast Cancer Survival

Role of Non-coding RNAs on the Radiotherapy Sensitivity and Resistance of Head and Neck Cancer: From Basic Research to Clinical Application

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