Targeting DNA repair pathways: mechanisms and potential applications in cancer therapy

Bai, Yongtai; Wang, Weibin; Wang, Jiadong

doi:10.1007/s42764-020-00026-7

Cited by 3 publications

(2 citation statements)

References 208 publications

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“…BER is the main mechanism that handles the spontaneous DNA damage caused by free radicals and other reactive species generated by metabolism. Furthermore, it corresponds to the main repair mechanism for small base changes in DNA, such as those caused by oxidation, alkylation, and deamination [29]. On the other hand, the NER mechanism is used to remove extensive lesions and to correct bases that distort the DNA double helix.…”

Section: Ionizing Radiationmentioning

confidence: 99%

An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome

Gonçalves

Pires

Marques

et al. 2022

Cancers

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Hereditary breast and ovarian cancer (HBOC) syndrome is a condition in which individuals have an increased risk of developing different types of cancer when compared to the general population. BRCA1 repair associated (BRCA1) and BRCA2 repair associated (BRCA2) genes are tumor suppressor genes that play a crucial role in cell, by repairing DNA damage. Mutations in these genes are responsible for 25% of HBOC cases. Individuals with this syndrome are often subjected to diagnostic imaging techniques, as well as therapeutic options, that use ionizing radiation, so it is crucial to understand whether these individuals may present higher radiosensitivity and, therefore, its consequences. Several studies have been carried out to understand if the exposure to different ionizing radiation doses can induce cancer in individuals with HBOC. Some of these studies have shown that individuals with HBOC are hypersensitive to the ionizing radiation and, therefore, have neoplasms resulting from mutations in genes that are important in maintaining genomic stability. When mutated, genes no longer guarantee this stability and promote the induction of carcinogenesis. Oppositely, other studies show that there is no association between exposure to ionizing radiation and an increased risk of developing cancer. Thus, the results are inconsistent, and there is a great need to clarify this relationship. In this review, we present the characteristics of HBOC syndrome and the effects that ionizing radiation can induce in individuals who have it. In addition, we review the studies that have already been carried out on this subject.

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Section: Ionizing Radiationmentioning

confidence: 99%

An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome

Gonçalves

Pires

Marques

et al. 2022

Cancers

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show abstract

“…The DNA damage response is a response that is commonly triggered by various exogenous and endogenous DNA lesions; its function is to maintain genomic integrity. A defective DNA damage response is an important hallmark of cancer ( 7 ). Defects in DNA damage repair pathways leading to the accumulation of genomic defects are closely linked to the initiation and progression of malignancies.…”

Section: Introductionmentioning

confidence: 99%

Determination of a DNA repair-related gene signature with potential implications for prognosis and therapeutic response in pancreatic adenocarcinoma

et al. 2022

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BackgroundPancreatic adenocarcinoma (PAAD) is one of the leading causes of cancer death worldwide. Alterations in DNA repair-related genes (DRGs) are observed in a variety of cancers and have been shown to affect the development and treatment of cancers. The aim of this study was to develop a DRG-related signature for predicting prognosis and therapeutic response in PAAD.MethodsWe constructed a DRG signature using least absolute shrinkage and selection operator (LASSO) Cox regression analysis in the TCGA training set. GEO datasets were used as the validation set. A predictive nomogram was constructed based on multivariate Cox regression. Calibration curve and decision curve analysis (DCA) were applied to validate the performance of the nomogram. The CIBERSORT and ssGSEA algorithms were utilized to explore the relationship between the prognostic signature and immune cell infiltration. The pRRophetic algorithm was used to estimate sensitivity to chemotherapeutic agents. The CellMiner database and PAAD cell lines were used to investigate the relationship between DRG expression and therapeutic response.ResultsWe developed a DRG signature consisting of three DRGs (RECQL, POLQ, and RAD17) that can predict prognosis in PAAD patients. A prognostic nomogram combining the risk score and clinical factors was developed for prognostic prediction. The DCA curve and the calibration curve demonstrated that the nomogram has a higher net benefit than the risk score and TNM staging system. Immune infiltration analysis demonstrated that the risk score was positively correlated with the proportions of activated NK cells and monocytes. Drug sensitivity analysis indicated that the signature has potential predictive value for chemotherapy. Analyses utilizing the CellMiner database showed that RAD17 expression is correlated with oxaliplatin. The dynamic changes in three DRGs in response to oxaliplatin were examined by RT-qPCR, and the results show that RAD17 is upregulated in response to oxaliplatin in PAAD cell lines.ConclusionWe constructed and validated a novel DRG signature for prediction of the prognosis and drug sensitivity of patients with PAAD. Our study provides a theoretical basis for further unraveling the molecular pathogenesis of PAAD and helps clinicians tailor systemic therapies within the framework of individualized treatment.

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Lactylation regulated DNA damage repair and cancer cell chemosensitivity

Liu,

Huang,

Liu

2024

Science Bulletin

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Targeting DNA repair pathways: mechanisms and potential applications in cancer therapy

Cited by 3 publications

References 208 publications

An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome

An Overview on Radiation Sensitivity in Hereditary Breast and Ovarian Cancer Syndrome

Determination of a DNA repair-related gene signature with potential implications for prognosis and therapeutic response in pancreatic adenocarcinoma

Lactylation regulated DNA damage repair and cancer cell chemosensitivity

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