P1, N=5, Not yet recruiting, University of Oklahoma

Sulconazole blocks glycolysis-driven PD-L1 expression and restores OVOL2 function, inducing PANoptosis and reversing immune evasion. Repurposing sulconazole offers a promising strategy for glycolytic, immunosuppressive CRC.

This study reveals crosstalk between autophagy and the Warburg effect in Saos-2 cells, where glycolytic stress triggers protective autophagy and its inhibition alters metabolism, promoting apoptosis.

It was established that DCBLD1 lactylation bound to PDIA3, contributing to oesophageal cancer malignancy and glycolysis.

Glucose uptake at sub-cytotoxic levels was quantified using the fluorescent analog 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino)-2-Deoxyglucose... These results demonstrate that phloretin selectively inhibits glucose uptake in liver cancer cells, likely through its high-affinity interaction with GLUT-2. Collectively, these findings highlight phloretin's potential as a metabolic therapeutic agent and support GLUT-2 as a viable target for HCC intervention.

The oncogenic phenotypes driven by TRIM47 overexpression on cellular viability and the cell cycle were counteracted by either administration of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG) or by forced expression of FBP1...As the core effector molecule in the lactic acid-H3K18la epigenetic circuit, TRIM47 drives tumorigenesis by inducing ubiquitin-mediated degradation of FBP1. Targeting of this signaling axis holds significant promise for the development of new thyroid cancer therapies.

Cell models were established in BEAS-2B and NSCLC cell lines, with lactylation regulated by lactate (LA) and 2-deoxyglucose (2-DG)...Mechanistically, β-catenin K193 lactylation reduced LPO and increased GSH to suppress ferroptosis: lactylated β-catenin translocated to the nucleus, formed a complex with TCF4, and upregulated GPX4 transcription by binding its promoter. GPX4 overexpression reversed ferroptosis induced by β-catenin K193 lactylation inhibition, while blocking β-catenin/TCF4 interaction downregulated GPX4 and enhanced ferroptosis.

The dual-targeting LNP@2DG-DON nanoparticle synergistically combines metabolic and immune modulation, demonstrating superior antitumor effects compared to single-agent therapies. This approach represents a promising strategy for pancreatic cancer treatment, warranting further clinical investigation.

PFKP is a critical link between glycolysis and immune suppression in HCC. It promotes immune checkpoint expression and mTOR activation, suggesting a role in immune evasion. PFKP represents a dual biomarker for prognosis and immunotherapy response, and a promising target for combined metabolic and immune-based therapies.

2-Deoxy-D-glucose (2DG), a glycolytic inhibitor, depleted ATP dose-dependently (30-300 μM) and prevented those increases both at the protein and transcriptional levels. This was also observed in 3D spheroids upon TGF-β transient siRNA-mediated silencing or when TGF-βR1 kinase activity was inhibited by galunisertib...3D spheroids require ATP and a TGF-β/TGF-βR1 autocrine signaling axis to recapitulate the apoptosis/autophagy phenotypes. Combining glycolysis inhibition with TGF-β signaling inhibition could offer a promising therapeutic strategy for this rare and lethal brain cancer.

Functionally, TBK1 promoted cell proliferation and colony formation while inhibiting apoptosis, which were attenuated by the glycolytic inhibitor 2-deoxy-D-glucose. These findings establish TBK1 as a critical mediator linking GM dysbiosis to metabolic reprogramming in CRC, suggesting that targeting the TBK1-glycolysis axis may represent a promising therapeutic strategy for delaying CRC progression.