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Citrate targets FBPase and constitutes an emerging novel approach for cancer therapy
Philippe Icard1, Ludovic Fournel2, Antoine Coquerel3
11Thoracic Surgery Department, Cochin Hospital, Normandy University of Caen, Unité Inserm 1199, Paris, France.
Abstract:
Gao-Min Liu and Yao-Ming Zhang recently published a review entitled «Targeting FBPase is an emerging novel approach for cancer therapy» (Liu and Zhang in Cancer Cell Int 18:36, 2018). In this paper, the authors highlighted how the down regulation or inactivation of FBPase, a rate limiting enzyme of gluconeogenesis, can promote the Warburg effect and cancer growth. In contrast, activation of this enzyme demonstrates anti-cancer effects and may appear as emerging novel approach for cancer therapy. Among the potential activators of FBP listed by Liu and Zhang, citrate was surprisingly not mentioned although it is an activator of FBPase, also demonstrating various anti-cancer effects in pre-clinical studies. Thus, citrate should be tested as a new therapeutic strategy, in particular in clinical studies.
Insights
Targeting Fructose-1,6-bisphosphatase (FBPase) is a novel cancer therapy approach. Activating FBPase, unlike its inactivation which promotes cancer, shows anti-cancer effects, suggesting citrate as a potential therapeutic agent.
Area of Science:
- Biochemistry
- Oncology
- Metabolic pathways
Background:
- Fructose-1,6-bisphosphatase (FBPase) is a key enzyme in gluconeogenesis.
- Its downregulation or inactivation promotes the Warburg effect and cancer progression.
- Conversely, FBPase activation exhibits anti-cancer properties.
Purpose of the Study:
- To highlight FBPase as an emerging therapeutic target for cancer.
- To propose citrate as a potential FBPase activator for cancer therapy.
- To advocate for clinical studies investigating citrate's anti-cancer effects.
Main Methods:
- Literature review of FBPase's role in cancer metabolism.
- Analysis of known FBPase activators and their therapeutic potential.
- Identification of gaps in current research regarding FBPase activators.
Main Results:
- FBPase inactivation is linked to increased Warburg effect and cancer growth.
- FBPase activation demonstrates significant anti-cancer effects.
- Citrate, a known FBPase activator, was notably absent from previous reviews of FBPase-targeting cancer therapies.
Conclusions:
- Targeting FBPase represents a promising strategy for novel cancer therapies.
- Citrate's properties as an FBPase activator warrant further investigation.
- Clinical evaluation of citrate is recommended to explore its therapeutic potential in cancer treatment.
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