Hereditary Pancreatic Cancer: Advances in Genetic Testing, Early Detection Strategies, and Personalized Management

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy with a five-year survival rate of approximately 13% for advanced stages. While the majority of PDAC cases are sporadic, a significant subset is attributable to hereditary and familial predispositions, accounting for approximately 25% of cases. This article synthesizes recent advancements in the understanding, detection, and management of hereditary pancreatic cancer (PC). Results: Our review highlights the critical role of genetic testing (GT) in identifying high-risk individuals (HRIs), with germline pathogenic variants (PVs) found in up to 20% of hereditary PDAC cases. Since the implementation of next-generation sequencing (NGS) panels in 2014, detection capabilities have been significantly enhanced. HRIs can be included in screening programs that facilitate the early detection of PDAC. Early detection strategies, including the use of microribonucleic acid (miRNAs) signatures and novel imaging techniques like hyperpolarized 13C-magnetic resonance spectroscopy (MRS) have shown promising results. The identification of germline pathogenic variants (PVs) or mutations in homologous recombination (HR) genes plays a predictive role in the response to various treatments, prolonging patient survival. Discussion: Universal germline testing for PDAC, as recommended by the National Comprehensive Cancer Network (NCCN), is now a standard practice, facilitating the identification of at-risk individuals and enabling targeted surveillance and intervention. Multidisciplinary management, integrating genetic counseling, imaging, and gastrointestinal services, is essential for optimizing outcomes. Conclusions: Advances in genetic testing and biomarker research are transforming the landscape of hereditary PC management. Early detection and personalized treatment strategies are pivotal in improving survival rates. Ongoing multi-institutional research efforts are crucial for validating biomarkers and developing preventive measures, ultimately aiming to reduce the burden of this aggressive cancer.