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• Tumor-agnostic treatments lead to the necessity of new pan-cancer biomarkers. • PARPi seems to offer a new chance in PDAC patients with disrupted DNA repair pathway. • MSI-H analysis guides the use of immunotherapy as new strategy in pancreatic cancer. • Inhibitors of KRAS G12C are promising tools for mutated pancreatic cancer patients. • Analysis of fusions in NRG1 and NTRK offers a new therapy opportunity to PDAC patients. Pancreatic cancer is one of the tumors with the worst prognosis, and unlike other cancers, few advances have been made in recent years. The only curative option is surgery, but only 15–20% of patients are candidates, with a high risk of relapse. In advanced pancreatic cancer there are few first-line treatment options and no validated biomarkers for better treatment selection. The development of targeted therapies in pancreatic cancer is increasingly feasible due to tumor-agnostic treatments, such as PARP inhibitors in patients with BRCA1 , BRCA2 or PALB2 alterations or immunotherapies in patients with high microsatellite instability/tumor mutational burden. In addition, other therapeutic molecules have been developed for patients with KRAS G12C mutation or fusions in NTRK or NRG1. Consequently, there has been a growing interest in biomarkers that may help guide targeted therapy in pancreatic cancer. Therefore, this review aims to offer an updated perspective on biomarkers with therapeutic potential in pancreatic cancer. [ABSTRACT FROM AUTHOR]