Contemporary insights into the molecular mechanisms of development and genetic susceptibility to pancreatic cancer

Background. Pancreatic cancer (PC) is an aggressive malignancy with a high mortality rate. Pancreatic ductal adenocarcinoma constitutes approximately 90 % of pancreatic cancers, and is frequently diagnosed at an advanced stage. The disease is distinguished by the presence of tumor micrometastasis prior to the onset of clinical symptoms, as well as rapid progression. There are currently no effective screening methods for the disease.

Aim of the study: analysis of available literature data about susceptibility genes and molecular mechanisms of PC.

Material and methods. The search for relevant sources was performed in the PubMed (NCBI), Elibrary, GoogleScholar, publications from January 2000 to December 2024 were included. Of the 959 papers analyzed, 60 were used to write the review, 27 of which were published in the last five years.

Results. Approximately 10 % of pancreatic adenocarcinoma patients are carriers of germinal pathogenic variants that cause an increased risk of PC. These variants predominantly occur in DNA damage repair genes. Tumor cells undergo complex multistep genetic alterations, and the accumulation of these changes facilitates the activation of various oncogenes that contribute to the progression of PC. Research in the field of molecular genetics makes it possible to identify groups of patients with certain genetic alterations who need to be prescribed targeted drugs.

Conclusion. This article provides an overview of current understanding of the genetic predisposition to PC. The functional/clinical significance of proteins involved in the pathogenesis of the disease was described. Genetic alterations of PC were discussed.

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