Abstract
Pancreatic cancer is one of the deadliest cancer types urgently requiring effective therapeutic strategies. Autophagy occurs in several compartments of pancreatic cancer tissue including cancer cells, cancer associated fibroblasts, and immune cells where it can be subjected to a multitude of stimulatory and inhibitory signals fine-tuning its activity. Therefore, the effects of autophagy on pancreatic carcinogenesis and progression differ in a stage and context dependent manner. In the initiation stage autophagy hinders development of preneoplastic lesions; in the progression stage however, autophagy promotes tumor growth. This double-edged action of autophagy makes it a hard therapeutic target. Indeed, autophagy inhibitors have not yet shown survival improvements in clinical trials, indicating a need for better evaluation of existing results and smarter targeting techniques. Clearly, the role of autophagy in pancreatic cancer is complex and many aspects have to be considered when moving from the bench to the bedside.
Highlights
Pancreatic cancer (PC) is one of most deadly cancer types mainly due to delayed diagnosis, high metastatic capacity, and aggressive local progression
This study proved that the effect of autophagy regulators in cancer might differ among different cancer types
The roles of autophagy and autophagic regulators differ during PC development and progression
Summary
Pancreatic cancer (PC) is one of most deadly cancer types mainly due to delayed diagnosis, high metastatic capacity, and aggressive local progression. In spite of therapeutic and diagnostic advances in other cancer types, clinical management of PC remains limited, crucially affecting patient health. Most frequent genetic alterations promoting pancreatic tumorigenesis include KRAS activation, TP53, CDKN2A, and SMAD4 mutation [2]. All of these genetic changes influence tumorigenesis in both a cell-autonomous and non-cell autonomous manner, affecting protein synthesis, cell growth, cell metabolism, and proliferation, collectively deranging cellular homeostasis. The researchers detected autophagy in Syrian hamsters after carcinogen-mediated PC induction [5]. This observation subsequently paved the way for the development of therapeutic approaches targeting autophagy. The importance of autophagy will be highlighted in the cancer core, and in the tumor micro- and macroenvironment
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