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Genomic instability, DNA damage response and telomere homeostasis in pancreatic cancer

. 2025 Aug ; 113 () : 59-73. [epub] 20250515

Language English Country Great Britain, England Media print-electronic

Document type Journal Article, Review

Pancreatic cancer (PC) is becoming one of the most serious health problems at present, but its causes and risk factors are still unclear. One of the drivers in pancreatic carcinogenesis is altered genomic (DNA) integrity with subsequent genomic instability in cancer cells. The latter comprises a) DNA damage response and DNA repair mechanisms, b) DNA replication and mitosis, c) epigenetic regulation, and d) telomere maintenance. In our review we addressed the above aspects in relation to the most abundant and severe form of PC, pancreatic ductal adenocarcinoma (PDAC). In summary, the interactions between the DNA damage response, telomere homeostasis and mitotic regulation are not comprehensively understood at present, including the epigenetic factors entering the trait of genomic stability maintenance. In addition, the complexity of telomere homeostasis in relation to PDAC risk, prognosis and prediction also warrants further investigations.

Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 Pilsen 32300 Czech Republic; Division of Cancer Epidemiology German Cancer Research Center Heidelberg FRG 69120 Germany

Biomedical Centre Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Mala Hora 4 Martin 03601 Slovakia

Biomedical Centre Martin Jessenius Faculty of Medicine in Martin Comenius University in Bratislava Mala Hora 4 Martin 03601 Slovakia; Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1655 Pilsen 32300 Czech Republic; Institute of Biology and Medical Genetics 1st Faculty of Medicine Charles University Albertov 4 Prague 12800 Czech Republic

Cancer Predisposition and Biomarkers Group Instituto de Investigacion Sanitaria de Santiago Santiago de Compostela Spain

Cancer Research Institute Biomedical Research Center Slovak Academy of Sciences Dubravska cesta 9 Bratislava 84505 Slovakia

Department of Biology University of Pisa Pisa 56123 Italy

Department of Oncology Olomouc University Hospital Zdravotniku 248 7 Olomouc 77900 Czech Republic

Institute of Experimental Medicine Czech Academy of Sciences Videnska 1083 Prague 4 14200 Czech Republic

Institute of Experimental Medicine Czech Academy of Sciences Videnska 1083 Prague 4 14200 Czech Republic; Department of Genetics and Microbiology Faculty of Science Charles University Prague 12800 Czech Republic

Institute of Experimental Medicine Czech Academy of Sciences Videnska 1083 Prague 4 14200 Czech Republic; Department of Physiology Faculty of Science Charles University Prague Czech Republic

References provided by Crossref.org

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