G6PD (Glucose-6-Phosphate Dehydrogenase)

A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose-response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models.

In vivo, RRx-001 significantly inhibits tumor growth, enhances T-cell infiltration, promotes M1 macrophage polarization, downregulates PD-L1 expression, and strengthens anti-tumor immunity through T cell-related pathways. With both metabolic and immunomodulatory effects, RRx-001 provides a basis for novel HCC therapies, and future research could explore its synergistic effects with immune checkpoint inhibitors.

Furthermore, we observed a positive correlation between G6PD overexpression and the resistance of CML cells to imatinib. Subsequent mechanistic investigations revealed that the complex formed by the interaction of phosphorylated STAT3 (p-STAT3) and hypoxia-inducible factor 1α (HIF-1α) functions as a novel transcriptional regulator of G6PD, thereby driving its increased expression. Collectively, this study provides compelling evidence that strategies directly targeting p-STAT3/HIF-1α-G6PD may represent an effective therapeutic approach to suppress CML cells proliferation and overcome drug resistance, offering new insights into the diagnosis and clinical management of CML patients.

Drug sensitivity prediction indicated that high-risk patients may respond better to agents such as Tozasertib and Navitoclax. This study establishes a robust, demethylation-driven six-gene signature that effectively stratifies HCC patients into distinct prognostic groups. The model integrates multi-omic insights into tumor biology and therapeutic vulnerability, providing a clinically actionable framework for personalized risk assessment and treatment planning in hepatocellular carcinoma.

This study reveals that bile acid metabolism promotes HCC progression by facilitating vascular network formation and establishing an immunosuppressive tumor microenvironment. The bile acid metabolism scoring system may serve as a novel prognostic biomarker and provide a theoretical foundation for developing precision therapeutic strategies in HCC.

SYP restored sorafenib sensitivity in resistant cells through G6PD inhibition. SYP enhances bevacizumab efficacy by targeting angiogenesis, ferroptosis, and G6PD-mediated resistance, providing a rationale for integrating traditional and modern therapies in HCC management. These findings highlight the value of network pharmacology in elucidating TCM mechanisms and support further clinical evaluation.

Importantly, treatment with G6PD inhibitor (G6PDi), a G6PDi reduced aggressiveness of PR KD cancer cells. These findings suggest that targeting G6PD could be a promising therapeutic strategy to suppress the aggressiveness of luminal breast cancer, using low PR expression as a biomarker.

Patients with G6PDd are susceptible to HEV infection. The facilitation of HEV entry and aggravation of oxidative stress may contribute to HEV susceptibility in patients with G6PDd and severe disease.

Importantly, the identification of CSV also provides a rationale for developing CSV-guided delivery systems, enabling targeted silencing of PVTT-associated molecular drivers such as G6PD. Collectively, our findings highlight G6PD+CSV+ CTCs as a dual-function biomarker for both PVTT risk stratification and treatment response monitoring, offering a novel strategy for the precision management of advanced HCC with PVTT involvement.

Induction of G6PD expression in FOXO1-deficient cells mitigates tumor growth inhibition and alleviates ROS level elevation. These results establish a critical role for FOXO1 in the regulation of G6PD during the antioxidative and proliferative processes of cancer cells.

These metabolic changes impaired tumor cell proliferation and sensitized ICC cells to cisplatin, emphasizing the dual therapeutic potential of targeting G6PD to inhibit tumor growth and overcome chemoresistance...Future research should explore the integration of enhancer profiling into precision medicine frameworks and the development of novel enhancer-targeting strategies. These efforts could uncover additional metabolic vulnerabilities and provide effective treatments for this highly aggressive cancer.