Pancreatic ductal adenocarcinoma (PDAC): clinical progress in the last five years

INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with limited therapeutic options and poor overall survival. In recent years, advances in genomic profiling have revealed the complex molecular and cellular heterogeneity of PDAC, offering new avenues for therapeutic intervention. AREAS COVERED: This review explores emerging therapeutic strategies targeting dysregulated molecular pathways, along with the tumor microenvironment, that have shown promise in overcoming drug resistance. Novel immunotherapy strategies, such as immune checkpoint inhibitors and CAR T-cell therapies, are currently being explored in an attempt to modulate PDAC immugnosuppressive microenvironment. Additionally, we highlight recent clinical trials over the last 5 years and innovative therapeutic strategies aiming to improve outcomes in PDAC. EXPERT OPINION: Significant progress in genomic profiling, targeted therapies, and immunotherapy is shaping the treatment of PDAC. Despite challenges posed by its dense stroma and immune suppressive microenvironment, novel strategies such as IL 6 and CD137 inhibitors, CAR-T, and therapeutic cancer vaccines are promising. KRAS targeted therapies are expanding beyond G12C inhibitors, with novel drugs in development that will further improve treatment options. Additionally, tumor treating fields (TTF) are being investigated in locally advanced PDAC, with the PANOVA-3 trial potentially integrating this modality into future treatment strategies. Continued advancements in these areas will significantly enhance PDAC outcomes.