EPAS1 (Endothelial PAS domain protein 1)

PGR activation in response to hormonal stimulation induced expression of a HIF reporter system in primary human granulosa cells, with HIF-2 inhibition with the small molecule PT-2385 confirming a HIF-2 contribution to this response...In particular, inflammatory gene expression was dysregulated and a cohort of gonadotrophin-dependent genes, including Pgr, were elevated, suggesting impaired downregulation post-ovulation. These findings provide an important insight into regulation of the hypoxia inducible transcription factors during ovulation and how targeting HIF-2α may be of benefit in future fertility treatments.

Importantly, combinatorial blockade of IGFBP2 and CD47 synergistically suppressed tumor growth and prolonged survival in orthotopic GBM models. Together, our findings uncovered the hypoxia-exosomal IGFBP2-CD47 axis in GBM immune evasion and provided a compelling rationale for combination therapy to improve immunotherapy efficacy in GBM.

The determination of affinity was accomplished using microscale thermophoresis (MST). Here, we describe a detailed protocol for the assessment of binding affinities between HIF2α peptides or the entire oxygen-dependent degradation domains of HIFα proteins and PHD2 using MST and propose that this method can be used to assess the potential pathogenicity of novel mutations in HIF2α.

Together, this study underscores the coordinated role of HIFα and ZNF395 in shaping metabolic adaptations in response to hypoxia in VHL-deficient ccRCCs. ZNF395 and HIF are complementary mediators of hypoxia-induced metabolic reprogramming and therapeutic targets in VHL-deficient kidney cancer, with the former regulating glutamine metabolism and the latter regulating glucose metabolism.

As reported, ongoing phase III clinical trials are set to yield potentially practice-changing results, investigating innovative combinatorial strategies including belzutifan. Ongoing advancement of predictive biomarkers and understanding of resistance mechanisms could improve patient selection and identify new drug targets, thereby increasing the clinical efficacy of belzutifan.

Despite extensive prior treatment, patients experienced clinical benefit from TT, particularly VEGFR-TKIs, after progression on belzutifan. These findings support the feasibility of sequencing TT following belzutifan-based regimens in advanced ccRCC, and highlight the need to further define optimal therapeutic sequencing strategies.

By expanding upon the foundation established by belzutifan, the field is poised for further therapeutic advances.

Upon ultrasound exposure as an "exogenous switch," activated Ce6, together with Vitamin K3 and Mn2+, induces a robust ROS storm, resulting in mitochondrial dysfunction and immunogenic cell death (ICD), while effectively reprogramming the chronic hypoxia-HIF-2α-driven immunosuppressive tumor microenvironment. Furthermore, in vivo studies demonstrated that Lenvatinib therapy, when combined with the nanoplatform, further suppressed chronic hypoxia-HIF-2α-driven abnormal angiogenesis, enhanced CD8+ T-cell infiltration, and boosted antitumor immune responses, ultimately achieving a potent synergistic therapeutic effect and promoting the conversion of "cold tumors" into "hot tumors." This study provides strong experimental evidence that nanoplatform-mediated immune microenvironment reprogramming represents a precisely controllable and highly effective therapeutic strategy for solid tumors, with promising translational potential in hepatocellular carcinoma.

An accumulation of hypoxia-inducible factor (HIF)-2α was associated with hypoxia-regulating miRNAs in sEVs from HNSCC patients. This provides new insights into a proposed tumor-associated systemic sEV-miRNA-mediated hypoxia transfer.

Moreover, treatment with NKT2152 significantly reduced tumor growth in both cell line-derived and patient-derived xenograft models. In conclusion, our findings provide novel insights into the prognostic and functional role of HIF2A in ovarian CCC and underscore its potential as a promising therapeutic target.

Hypoxia is a crucial factor that triggers the switch of angiogenesis and other inflammatory mediators, facilitating tumorigenesis. This is essential for anticipating the malignant conversion of epithelial dysplasia and, in turn, also predicts the prognosis.

Despite standard treatments such as surgical resection and chemoradiotherapy, overall survival (OS) usually does not exceed 14-16 months in clinical trials, and no improvement in OS has been demonstrated even with the use of vascular endothelial growth factor A (VEGFA) inhibitors such as bevacizumab...Several clinical trials evaluating HIF-2α inhibitors as monotherapy in the absence of concurrent VEGF inhibition, have similarly failed to demonstrate a significant improvement in OS outcomes. This review provides a perspective on the combined use of VEGF and HIF inhibitors, and provides an insight into future studies.