EPAS1 (Endothelial PAS domain protein 1)

Resistance to HIF-2α inhibitors such as Belzutifan underscores the need to better understand how HIF-2α is transcriptionally regulated in clear cell renal cell carcinoma (ccRCC)...Unlike prior studies focusing on VHL/HIF occupancy-driven enhancer activation, this work defines a trans-acting cytokine-JAK1-STAT3 pathway that transcriptionally controls EPAS1. Together, these findings reveal a targetable enhancer mechanism that sustains HIF-2α expression and suggest that combined inhibition of JAK1/STAT3 and HIF-2α may overcome therapeutic resistance in kidney cancer.

Translational entry points include selective HIF-2α inhibition, phosphoinositide 3-kinase gamma (PI3Kγ) blockade, SUCNR1 targeting, and exosome-based miRNA modulation, while a biomarker panel comprising HIF-1α, vascular endothelial growth factor A (VEGF-A), and MMP-9 offers a pragmatic readout of hypoxia burden, macrophage programming, and therapeutic response. We conducted a focused narrative review (PubMed, Scopus, Web of Science; English; 2003-2025), prioritizing mechanistic and translational studies on hypoxia-HIF, lactate/succinate, and hypoxia-regulated exosomes across T2D, atherosclerosis, and cancer.

Our in vitro findings indicate that AHCY suppresses ferroptosis, partly via the Hippo-YAP pathway, thereby promoting the invasion and migration of NPC cells. Further in vivo and clinical studies are warranted to validate these findings.

This review elucidates the molecular regulatory mechanisms of the HIF-2α-EPO-Hb axis, delineates its dysregulation in chronic hypoxic diseases and tumorigenesis, and evaluates current research progress and clinical limitations of related therapies. The discussion provides theoretical foundations and future perspectives for mechanistic research and clinical intervention in relevant diseases.

In our study, the PR-619 inhibitor caused a decrease in the HIF2α protein level in 786-O, OS-RC-2, and SW839 cells, and MG132 treatment increased HIF2α protein expression after PR-619 treatment...We also confirmed that USP10 expression was upregulated in kidney cancer and had a positive correlation with HIF2α expression in RCC patient samples. Our results suggest that USP10 promotes HIF2α stability.

When combined with the PD-1 inhibitor pembrolizumab as an adjuvant treatment, it reduced the risk of disease recurrence by 28% and prolonged disease-free survival over pembrolizumab alone. For patients whose disease returned following immunotherapy, belzutifan and the VEGFR inhibitor lenvatinib bested the VEGFR inhibitor cabozantinib in overall response, progression-free survival, and duration of response.

This study provides statistical and genetic evidence that HAA is a causal risk factor for HCC in Tibetans. The identification of HAA-related genes in HCC tissues offers new insights for targeted prevention and treatment strategies in Tibetan populations.

Its sensitivity for predicting tumor metastasis/recurrence is higher than that of GAPP, while its specificity is higher than that of PASS. The combined use of negative SDHB and S-100 protein expression with COPPS could be used to stratify the risk of metastasis/recurrence in PPGL.

US Food and Drug Administration-approved DNMT inhibitors, such as decitabine and azacitidine, and investigational agents including RX-3117 and SGI-1027 selectively suppressed the growth of VHL-deficient RCC cells. Further mechanistic analysis showed that KCNK3 reactivation triggers TNF-α, MAPK and apoptotic signaling pathways, contributing to the observed synthetic lethality. Collectively, these findings establish DNMT inhibition as a synthetic lethal strategy in VHL-deficient RCC and highlight a potential therapeutic vulnerability for personalized treatment approaches.

P1, N=40, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business decision and not related to safety concerns

This phenomenon is reversible with the epitranscriptomic compound 5-azacytidine. Consistent with these findings, IP expression is excluded from hypoxic regions in most human NSCLC tumors. Together, these results link tumor hypoxia to a state of "immunogenic dormancy" and identify stress granules as a previously unrecognized mechanism of immune escape.

This study investigated the impact of adding pioglitazone to imatinib therapy in 26 newly diagnosed chronic-phase CML patients. No abstract available