The current understanding of mitochondrial metabolism in cancer is limited, and its therapeutic potential is not fully exploited

The gap

Evidence profile

Sourced from the future work and stated research gap of the source papers, classified as general, drawn from work published between 2024 and 2026, spanning 3 journals. Those papers have been cited 228 times in total.

Supporting evidence — 3 representative gaps

• The PI3K/Akt Pathway and Glucose Metabolism: A Dangerous Liaison in Cancer (2024) · International Journal of Biological Sciences · cited 228× · doi

  be on should focused A growing body of evidence suggests that aberrant activation of the PI3K/Akt cascade drives tumor initiation and progression via a profound rewiring of glucose metabolism. In this context, future studies a deeper characterization of the critical regulatory nodes connecting this signaling to the glycolytic flux in different malignancies, to identify new metabolic dependencies and vulnerabilities. On the other side, the interactions between the PI3K/Akt pathway and other glycolysis-related metabolic networks should be investigated, to develop a broader view of the tumorigenic constitutive implications of Akt phosphorylation. Indeed, metabolic enzymes are inherently represent fundamental therapeutic hotspots, due to their role as essential modulators of cancer cell proliferation and survival. druggable could and Table 1. Main drugs targeting glycolysis in cancer.

  generalfuture work
  Keywords: metabolic glycolysis cancer focused growing body evidence suggests aberrant activation cascade drives tumor initiation progression
• Histone deacetylases in cancer metabolic reprogramming (2026) · Experimental & Molecular Medicine · doi

  The intricate interplay between metabolism and epigenetics represents a rapidly evolving area in cancer research, offering important insights into how cellular metabolic states influence In this review, we gene regulation and tumour progression. focused on HDAC-mediated regulation of cancer metabolic reprogramming, with particular emphasis on glucose, lipids and amino acid metabolism. Across multiple aspects of carbohydrate metabolism, including gluconeogenesis, glycogen metabolism, glycolysis, PPP and mitochondrial metabolism, HDACs exert multi-layered regulatory functions. Through this regulation, HDACs modulate metabolic enzymes (e.g. HK, FBP1, GS), key metabolites and transcription factors such as c-Myc, thereby influencing cellular signalling networks52,58 (Fig. 7). Consistent with these observations, numer- ous studies have demonstrated that HDAC inhibitors disrupt glycolytic metabolism and suppress metastasis and tumour progression. the regulatory functions of HDACs extend beyond carbohydrate metabolism to encompass lipid and amino acid metabolic pathways that are essential for tumour growth and adaptation. HDAC1, HDAC3, HDAC5 and HDAC6 are major regulators of lipid metabolism through the regulation of FAO and FAS in cancer and are associated with a poor prognosis. In glutamine metabolism, HDAC6 has been shown to regulate GS activity and stability, thereby supporting cancer-cell survival under Importantly, Experimental & Molecular Medicine Y.H. Jeon et al. 11 Fig. 7 Integrated network of histone deacetylase-driven metabolic reprogramming in cancer. This integrated model summarizes how histone deacetylase (HDAC) isoforms coordinate glucose, lipid and amino acid metabolism in cancer cells, including glycolysis, the pentose phosphate pathway (PPP), the tricarboxylic-acid (TCA) cycle, oxidative phosphorylation (OXPHOS), fatty-acid oxidation (FAO), fatty-acid synthase (FAS) and glutamine metabolism. The network highlights metabolic intermediates that are regulated by HDACs and can be targeted by HDAC inhibitors. MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; TSA, trichostatin A; UFA, unsaturated fatty acid. metabolic stress16. Collectively, these findings indicate that class I HDACs (HDAC1, HDAC2, HDAC3 and HDAC8) and class II HDACs (HDAC5, HDAC6 and HDAC7) play critical roles in cancer- associated metabolic reprogramming (Table 1). Despite extensive research, most studies to date have primarily focused on the broad anticancer effects of pan-HDAC inhibitors rather than on the isoform-specific molecular mechanisms by which individual HDACs regulate metabolic enzymes and discrete steps within metabolic pathways (Table 2). Consequently, although HDAC inhibitors are well documented to suppress cancer-cell prolifera- tion and survival, the therapeutic potential of selectively targeting individual HDAC isoforms remains largely unexplored, particularly in the context of metabolic regulation. Thus, the development of isoform-sp

  generalfuture work
  Keywords: hdac metabolism metabolic acid cancer hdacs regulation fatty inhibitors tumour reprogramming amino lipid cellular progression
• Mitochondrial metabolic plasticity in cancer: hybrid bioenergetic states and translational targeting in surgical oncology (2026) · Experimental Biology and Medicine · doi

  The current understanding of mitochondrial metabolism in cancer is limited, and its therapeutic potential is not fully exploited. There is a need for a comprehensive review of the current knowledge on mitochondrial metabolic phenotypes in cancer and their relevance to therapeutic targeting. The relationship between glycolysis and oxidative phosphorylation in cancer is not fully understood.

  generalstated research gapevidence 5/5
  Keywords: current understanding mitochondrial metabolism cancer limited therapeutic potential

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