Glycometabolic rearrangements-aerobic glycolysis in pancreatic ductal adenocarcinoma (PDAC): roles, regulatory networks, and therapeutic potential

Introduction: Glycometabolic rearrangements (aerobic glycolysis) is a hallmark of pancreatic ductal adenocarcinoma (PDAC) and contributes to tumorigenesis and progression through numerous mechanisms. The targeting of aerobic glycolysis is recognized as a potential therapeutic strategy which offers the possibility of improving treatment outcomes for PDAC patients. Areas covered: In this review, the role of aerobic glycolysis and its regulatory networks in PDAC are discussed. The targeting of aerobic glycolysis in PDAC is examined, and its therapeutic potential is evaluated. The relevant literature published from 2001 to 2021 was searched in databases including PubMed, Scopus, and Embase. Expert opinion: Regulatory networks of aerobic glycolysis in PDAC are based on key factors such as c-Myc, hypoxia-inducible factor 1 alpha, the mammalian target of rapamycin pathway, and non-coding RNAs. Experimental evidence suggests that modulators or inhibitors of aerobic glycolysis promote therapeutic effects in preclinical tumor models. Nevertheless, successful clinical translation of drugs that target aerobic glycolysis in PDAC is an obstacle. Moreover, it is necessary to identify the potential targets for future interventions from regulatory networks to design efficacious and safer agents.

Automated summary

Aerobic glycolysis plays a crucial role in PDAC, with regulatory networks involving key factors such as c-Myc, HIF-1α, mTOR pathway, and non-coding RNAs. Experimental evidence suggests that modulators or inhibitors of aerobic glycolysis have therapeutic effects in tumor models, yet clinical translation remains a challenge.