Enhancing chemosensitivity in pancreatic cancer: novel strategies to overcome therapeutic resistance

Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and fatal malignancies, with a 5-year survival rate of <15%. Despite significant advancements in targeted therapies and immunotherapy, these approaches benefit only a limited subset of patients, leaving chemotherapy as the primary treatment modality for most patients. Chemotherapy is an essential adjunct to surgical resection, the only potentially curative option, playing a crucial role in reducing the tumor burden, delaying disease progression, and alleviating symptoms. However, its long-term efficacy is frequently undermined by the development of chemoresistance, wherein tumor cells adopt diverse strategies to evade or repair chemotherapy-induced damage. Addressing this critical barrier is imperative for improving the clinical outcomes of PDAC. This review comprehensively examines the multifaceted mechanisms of chemoresistance in PDAC and highlights innovative strategies designed to enhance chemosensitivity, thereby offering new hope for overcoming these challenges and improving patient survival.