The impact of DNA damage response gene polymorphisms on therapeutic outcomes in late stage ovarian cancer

Guffanti, Federica; Fruscio, Robert; Rulli, Eliana; Damia, Giovanna

doi:10.1038/srep38142

Cited by 10 publications

(5 citation statements)

References 52 publications

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“…Chk1 and Chk2 are the most important signal transducers for cell cycle regulation and DNA damage checkpoint responses 34 . In order to explore the mechanism of 1–3 induced S-phase arrest, the cell cycle-related proteins were evaluated by Western blotting and RT-PCR assay.…”

Section: Resultsmentioning

confidence: 99%

Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

Qin

Shen

Chen

et al. 2017

Sci Rep

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Three new oxoaporphine Co(II), Ni(II) and Zn(II) complexes 1–3 have been synthesized and fully characterized. 1–3 have similar mononuclear structures with the metal and ligand ratio of 1:2. 1–3 exhibited higher cytotoxicity than the OD ligand and cisplatin against HepG2, T-24, BEL-7404, MGC80–3 and SK-OV-3/DDP cells, with IC50 value of 0.23−4.31 μM. Interestingly, 0.5 μM 1–3 significantly caused HepG2 arrest at S-phase, which was associated with the up-regulation of p53, p21, p27, Chk1 and Chk2 proteins, and decrease in cyclin A, CDK2, Cdc25A, PCNA proteins. In addition, 1–3 induced HepG2 apoptosis via a caspase-dependent mitochondrion pathway as evidenced by p53 activation, ROS production, Bax up-regulation and Bcl-2 down-regulation, mitochondrial dysfunction, cytochrome c release, caspase activation and PARP cleavage. Furthermore, 3 inhibited tumor growth in HepG2 xenograft model, and displayed more safety profile in vivo than cisplatin.

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Section: Resultsmentioning

confidence: 99%

Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

Qin

Shen

Chen

et al. 2017

Sci Rep

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“…The identification of markers is also important to select patients for proper therapy. A polymorphism study on CDK12, which modulates the transcription elongation of RNA polymerase II and affects the expression of DDR genes, reveals it is a possible prognostic biomarker in late-stage ovarian cancer treated with platinum [355]. Markers that predict sensitivity or resistance to induced DNA damage therapy such as the Schlaffen biomarker are useful to predict the accurate response to Top1 and Top2 inhibitors, in colon and ovarian cancers [356].…”

Section: Pharmacogenomic and Predictive Markers In Ddr Strategiesmentioning

confidence: 99%

Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Molinaro

Martoriati

Cailliau

2021

Cancers

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Cells respond to genotoxic stress through a series of complex protein pathways called DNA damage response (DDR). These monitoring mechanisms ensure the maintenance and the transfer of a correct genome to daughter cells through a selection of DNA repair, cell cycle regulation, and programmed cell death processes. Canonical or non-canonical DDRs are highly organized and controlled to play crucial roles in genome stability and diversity. When altered or mutated, the proteins in these complex networks lead to many diseases that share common features, and to tumor formation. In recent years, technological advances have made it possible to benefit from the principles and mechanisms of DDR to target and eliminate cancer cells. These new types of treatments are adapted to the different types of tumor sensitivity and could benefit from a combination of therapies to ensure maximal efficiency.

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“…Moreover, we did not find information on testing polymorphisms of other DNA repair genes, i.e., XRCC6 , CHK1 , XPA , ERCC3/XPB , NEIL-2 , NTH-1 , and FEN-1 , although they were tested in other types of cancer. While CHK2 polymorphisms have been extensively studied in thyroid cancer, there is a lack of reports on CHK1 polymorphisms, which have been studied in nasopharyngeal cancer (NPC) and ovarian cancer [ 123 , 124 ]. The rs492510 CHK1 polymorphism increased the transcriptional activity of the CHK1 protein along with functionality, contributing to increased susceptibility to NPCs.…”

Section: Discussionmentioning

confidence: 99%

Polymorphisms of DNA Repair Genes in Thyroid Cancer

Gielecińska,

Kciuk,

Kołat

et al. 2024

IJMS

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The incidence of thyroid cancer, one of the most common forms of endocrine cancer, is increasing rapidly worldwide in developed and developing countries. Various risk factors can increase susceptibility to thyroid cancer, but particular emphasis is put on the role of DNA repair genes, which have a significant impact on genome stability. Polymorphisms of these genes can increase the risk of developing thyroid cancer by affecting their function. In this article, we present a concise review on the most common polymorphisms of selected DNA repair genes that may influence the risk of thyroid cancer. We point out significant differences in the frequency of these polymorphisms between various populations and their potential relationship with susceptibility to the disease. A more complete understanding of these differences may lead to the development of effective prevention strategies and targeted therapies for thyroid cancer. Simultaneously, there is a need for further research on the role of polymorphisms of previously uninvestigated DNA repair genes in the context of thyroid cancer, which may contribute to filling the knowledge gaps on this subject.

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The impact of DNA damage response gene polymorphisms on therapeutic outcomes in late stage ovarian cancer

Cited by 10 publications

References 52 publications

Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

Oxoaporphine Metal Complexes (CoII, NiII, ZnII) with High Antitumor Activity by Inducing Mitochondria-Mediated Apoptosis and S-phase Arrest in HepG2

Proteins from the DNA Damage Response: Regulation, Dysfunction, and Anticancer Strategies

Polymorphisms of DNA Repair Genes in Thyroid Cancer

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