Epidemiology and geographic distribution of BRCA1-2 and DNA Damage response genes pathogenic variants in pancreatic ductal adenocarcinoma patients.

Incidence of pancreatic ductal adenocarcinoma (PDAC) is increasing over the last years, while patients prognosis remains grim. Recently germline BRCA1 and 2 pathogenic variants (gBRCA1-2) have emerged as risk factors for PDAC development, as well as new predictors of response to specific therapeutic interventions. However, data on gBRCA1-2 incidence in PDAC are currently sparse and limited to selected categories of patients, as for positive cancer history cases, for patients affected only by early or late stages of disease and mainly from the North-American population, thus generating incomplete information about the gBRCA1/2 epidemiology.

Treatment opportunities and future perspectives for pancreatic cancer patients with germline BRCA1-2 pathogenic variants.

Personalized treatments and predictive biomarkers of pancreatic cancer (PDAC) are still lacking. Recently germline mutations in BRCA 1 and 2 genes, leading to homologous repair deficiency, have emerged as new targets for more specific and effective therapies, exploiting the increased susceptibility to platinum salts and PARP inhibitors. In addition to BRCA, pathogenic variants in PALB2 and in other genes involved in the DNA damage response pathway (DDR) represent potential targets, as well as their respective somatic alterations.