PFKFB4 (6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 4)

Four mannose metabolism-related prognostic genes were identified in BLCA, and macrophages were confirmed as critical cells. These findings provide valuable insights for improving prognostic assessment in BLCA.

Collectively, our findings demonstrate that RBM15 stabilizes PFKFB4 expression in BC through an m6A-IGF2BP3-dependent mechanism and thus promotes the glycolysis and inhibits CD8+ T cell function. Targeting RBM15 sensitizes tumors to PD1 blockade and provides a promising therapeutic strategy for BC.

These findings identify a previously unrecognized function of PFKFB4 in GC, extending beyond its canonical metabolic roles to include active regulation of ferroptosis, thereby promoting cancer progression. Consequently, pharmacological inhibition of PFKFB4 represents a promising therapeutic avenue for overcoming ferroptosis resistance and suppressing tumor progression in gastric cancer.

PFKFB4 shows therapeutic potential as a target for GBM treatment, and its inhibitor 5MPN significantly inhibits glycolysis and invasiveness in GBM. This study provides new insights and potential drug options for targeted therapy in GBM.

These findings unveil PFKFB4-glycolysis-EMT axis as a druggable vulnerability in PC metastasis and position bruceine A as a potential first-in-class, dual-function agent that simultaneously suppresses tumor growth and dissemination through metabolic reprogramming.

In this study, six mitochondrial energy metabolism-related prognosis biomarkers (COX7B, PPARGC1B, NDUFA11, PFKFB4, NDUFV2, and NDUFA7) were screened. A risk model was developed to provide a new reference for the prognosis of ccRCC patients.

However, manipulation of ncRNA expression causes significant changes in the tumor response, which suggests a therapeutic response. This study shows that the use of animal models is essential for exploring the molecular mechanisms of cancer and establishing new therapeutic approaches.

Moreover, the presence of PFKFB4-ΔEx6 notably sensitized HCC cells to everolimus both in vitro and in subcutaneous models (n = 8, p <0.01)...Given the clinical importance of mTOR/AKT inhibitors, PFKFB4-ΔEx6 could act as a predictive marker for treatment response, paving the way for personalized therapeutic strategies in HCC. These findings provide new insights into the functional diversity of glycolytic enzymes in cancer biology and targeted therapy.

cPFKFB4, a protein encoded by hypoxia-responsive circular RNA, facilitates the proliferation and metastasis of PC cells under hypoxic conditions by regulating PKM2-mediated glycolysis. Our findings not only offer fresh standpoints and valuable insights into the crosstalk between hypoxia, glucose metabolism reprogramming, and PC, but also provide a potential biomarker and therapeutic target for the treatment of PC.

These results underscore the oncogenic role of PFKFB4 in enhancing the Warburg effect and promoting malignant phenotypes in GBM, and support its potential as a therapeutic target for GBM treatment.

In vivo, compound 2v achieved significant tumor growth inhibition in the MDA-MB-231 human breast cancer xenograft model in female BALB/c-nu nude mice, with a tumor growth inhibition (TGI) rate of 71.9 % at 30 mg/kg/day. Collectively, these findings establish the NBD scaffold as a valuable pharmacophore for developing novel PFKFB4 inhibitors for anticancer applications.

The findings suggest that SP1 is a critical regulator of PDAC initiation and progression through its control of metabolic remodeling. Targeting SP1 and PFKFB4 represents a promising therapeutic strategy for PDAC treatment.