Mechanistic insights and therapeutic strategies for targeting autophagy in pancreatic ductal adenocarcinoma

Pancreatic ductal adenocarcinoma (PDAC) is characterised by early metastasis and resistance to anti-cancer therapy, leading to an overall poor prognosis. Macroautophagy (hereinafter referred to as autophagy) is a conserved cellular homeostasis mechanism that degrades various cargoes (e.g., proteins, organelles, and pathogens) mainly playing a role in promoting survival under environmental stress. Autophagy is an essential defense mechanism against PDAC initiation, acting on multiple levels to maintain cellular and tissue homeostasis. However, autophagy is also intimately involved in the molecular mechanisms driving PDAC progression, facilitating the adaptation of cancer cells to the tumor microenvironment's harsh conditions. In this review, we examine the complex role of autophagy in PDAC and assess the potential of modulating autophagy as a therapeutic strategy. By reviewing current research and clinical trials, we seek to elucidate how targeting autophagy can disrupt PDAC tumor survival mechanisms, enhance the efficacy of existing treatments, and ultimately improve patient outcomes.