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

ABSTRACT

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 1α, 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.

KEYWORDS:

• Pancreatic cancer
• aerobic glycolysis
• key enzymes
• c-Myc
• HIF-1Α
• signaling pathways
• Non-coding RNAs

Article highlights

• Enhancement of aerobic glycolysis in PDAC can promote tumor proliferation, invasion, metastasis, and therapy resistance.

• The important factors in the glycolytic regulatory networks of PDAC include c-Myc, hypoxia-inducible factor 1α, the mammalian target of rapamycin pathway, and non-coding RNAs.

• Preclinical studies targeting aerobic glycolysis have shown promising results in PDAC, indicating the potential role of these inhibitors as antineoplastic agents.

• Clinical trials are required to follow up on the promising results from preclinical studies with inhibitors of key glycolytic enzymes.

• Taking advantage of regulatory networks to identify other potential targets of future interventions will be a challenge.

• Further research should concentrate on how regulatory mechanisms associated with aerobic glycolysis are interconnected and linked to signaling pathways

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.