Selvi Saba, Real Carmen Macías, Gentiluomo Manuel, Balounova Katerina, Vokacova Klara, Cumova Andrea, Mohlenikova-Duchonova Beatrice, Rizzato Cosmeri, Halasova Erika, Vodickova Ludmila, Smolkova Bozena, Hemminki Kari, Campa Daniele, Vodicka Pavel
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.
Cancer Predisposition and Biomarkers Group, Instituto de Investigacion Sanitaria de Santiago, Santiago de Compostela, Spain.
Semin Cancer Biol. 2025 Aug;113:59-73. doi: 10.1016/j.semcancer.2025.05.005. Epub 2025 May 15.
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.
胰腺癌（PC）正成为当前最严重的健康问题之一，但其病因和风险因素仍不明确。胰腺致癌过程中的驱动因素之一是基因组（DNA）完整性改变，随后癌细胞出现基因组不稳定。后者包括：a）DNA损伤反应和DNA修复机制；b）DNA复制和有丝分裂；c）表观遗传调控；d）端粒维持。在我们的综述中，我们探讨了上述与最常见且最严重形式的胰腺癌——胰腺导管腺癌（PDAC）相关的方面。总之，目前对DNA损伤反应、端粒稳态和有丝分裂调控之间的相互作用尚未完全理解，包括参与维持基因组稳定性特征的表观遗传因素。此外，端粒稳态与PDAC风险、预后和预测相关的复杂性也值得进一步研究。
