Our findings indicate that CRIP1 knockdown induces a glycolytic switch in AML cells, rendering them exquisitely sensitive to glycolytic inhibition by 2-DG. This suggests that CRIP1 status could serve as a biomarker for predicting response to metabolic therapies and highlights 2-DG as a promising therapeutic agent for a subset of AML characterized by glycolytic dependency.

This study revealed a novel mechanism in which BMAL1 downregulation under aging and HFD conditions promotes NASH progression by binding to HIF-1α and modulating the glycolysis-NLRP3 inflammasome axis.

Importantly, the pharmacologic inhibition of glycolysis with 2-deoxy-d-glucose restored SOCS3 secretion in these AMs. Together, our findings demonstrate that lung tumor-associated AMs undergo a time-dependent metabolic shift toward glycolysis, resulting in impaired SOCS3 secretion-a phenotype that can be reversed by targeting glycolytic flux. These results highlight a potential therapeutic approach for modulating immune suppression in the tumor microenvironment.

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.