Druggable targets in pancreatic adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is a leading cause of cancer-related death worldwide. It is often diagnosed at an advanced or metastatic stage and results of the approved systemic therapies are discouraging, making PDAC one of most lethal cancers in Western countries. In recent years, a better comprehension of PDAC unique biology has disclosed new potential targets for therapeutic interventions. Meanwhile, the development of conjugated agents, small molecules, antibodies, and immunoagents has opened therapeutic opportunities for drugs able to exert therapeutic effects on druggable targets of PDAC biology. Despite some failures, this approach is bringing meaningful results from bench to bedside, and more efficacious therapeutic opportunities may become available for PDAC treatment. In this review, we discuss the main hallmarks of PDAC biology as its microenvironment, cancerdriving proliferative pathways, growth suppression loops, and how PDAC evades immune system surveillance, as well as molecular aspects of each feature. The main preclinical and clinical results of each targeted intervention are also presented considering its biological rationale. Ongoing clinical trials provide evidence of the effectiveness of this approach and promising results in the treatment of PDAC.