Advanced multimetabolic APTw-CEST and 2-deoxy-D-glucose-CEST postprocessing metrics allowed adequate preclinical murine BC subtyping. AREX showed potential for 2-deoxy-D-glucose-CEST in tumor characterization; however, APTw-CEST remains superior. MTRasym failed to distinguish between tumor subtypes in CEST-MRI.

In vivo, NAT10 promoted tumor growth. Collectively, NAT10 contributes to RB progression by enhancing glycolysis through ac4C-mediated PFKFB3 mRNA stabilization, identifying the NAT10-ac4C-PFKFB3 axis as a potential therapeutic target.

Lactylation at K873 stabilized HK2 by inhibiting its ubiquitination, which in turn drove glycolytic flux and promoted malignant behaviors in DDP-resistant NSCLC. This HK2 lactylation-stabilization axis represents a novel mechanism underlying chemoresistance and a promising therapeutic target for overcoming DDP resistance in NSCLC.

While early HK2 inhibitors like 2-Deoxy-d-glucose (2-DG), and 3-Bromo pyruvic acid (3-BP) showed potential, their clinical utility was limited by off-target effects...These compounds were screened for HK2 inhibitory activity, followed by structural optimization to enhance selectivity and efficacy in in vitro and in vivo models of OSCC. Our findings identified a novel BTZ-based HK2 inhibitor compound 12 with HK2 IC50 of 56 nM and a ∼50-fold improvement in HK2 inhibitory potency over initial lead compound H2, that not only exhibits potent anti-cancer activity but also induces mitophagy, providing a new mechanism for OSCC therapy.

Based on these findings, the combined use of 2DG with BAD BH3 mimetic have proven effective against various types of cancer cells. In conclusion, this study provides a theoretical basis and rationale for the combined use of 2DG and BH3 mimetics as a promising therapeutic strategy for cancers.

These findings identified a novel metabolic-inflammatory axis (cAMP/PKA-HK2-caspase-3/GSDME) in breast cancer. Furthermore, study highlights the in vivo efficacy and safety of 2-DG and its ability to induce pyroptosis, thereby providing a basis for targeting drug resistance in breast cancer.

Inhibition of tumor immune evasion has also been explored using glycolytic enzyme inhibitors, including 2-deoxy-D-glucose and oxalate. Despite these advances, lactylation-targeted research remains in its early stages and faces notable limitations that warrant further investigation. This review provides insights into the role of lactylation in diverse diseases and highlights emerging therapeutic strategies aimed at modulating lactylation-associated molecular targets.

These findings identify H3K18la-mediated FOXM1 activation as a novel mechanism underlying DTX resistance in PCa. Ica-Cur may represent a promising therapeutic agent by targeting lactylation-dependent epigenetic regulation and FOXM1-driven transcriptional activity, supporting its clinical potential for overcoming chemoresistance.

QJZG effectively improved renal injury in SLE by reducing inflammation and modulating the AMPK/ULK1 signalling pathway to suppress M1 macrophage polarisation.

Background/Objectives: Melanoma cells enhance glycolysis and expand lysosomes to support energy metabolism, proliferation, and metastasis. However, mefloquine and siramesine induced stronger LMP in A375 cells than in fibroblasts and showed melanoma-selective toxicity when combined with 2DG. 2DG-mediated glycolysis inhibition in combination with lysosomal destabilization induced by mefloquine and siramesine, but not with non-selectively toxic LLOMe, may be promising antimelanoma strategy.

The impact of glycolytic inhibition by 2-Deoxy-D-glucose (2-DG) on CAR-NK92 antitumor capacity was examined...Conclusion ATPIF1 regulates the antitumor activity of CAR-NK92 cells through modulating glycolytic metabolism. Overexpression of ATPIF1 can enhance the antitumor efficacy of CAR-NK92 cells.

This was achieved using 2-deoxy-D-glucose (2DG) alone, 2DG combined with metformin, or Poly(2-hydroxyethyl methacrylate) (polyHEMA)-coated surfaces. These clones also demonstrated enhanced detachment properties and upregulation of proto-oncogenes, in addition to their senescent-like phenotype. Critically, the uncoupling of CD274 transcription from surface PD-L1 expression suggests a potential therapeutic vulnerability that could be exploited in TNBC.