EPAS1 (Endothelial PAS domain protein 1)

As agriculture faces mounting pressures from climate change and environmental stressors, deeper understanding of HIFs will be critical for sustaining productivity, improving animal welfare, and guiding future breeding and management strategies. This article is a narrative review summarizing current knowledge and recent advances of HIF biology across livestock species.

The effect of these compounds on HIF-2α expression was evaluated using a laboratory-developed 786-O/HRE reporter cell line, which was designed for screening of bioactive compounds targeting HIF-2α signaling in ccRCC. As a result, compounds 8-11 suppressed HIF-2α expression without apparent cytotoxicity and further inhibited HIF-2α-regulated endothelial cell tube formation at 5 μM.

The NK cell/PDO co-culture platform allows the identification of both common and patient-specific impacts of the tumor microenvironment on NK cell function and can aid the development of patient-tailored immunotherapies. The majority of CRC (CMS2/CMS3) PDOs from our cohort were susceptible to NK cell-mediated killing and induced NK cell activation, highlighting the potential of NK cells for CRC immunotherapies.

Therefore, a combination of drugs targeting hypoxia signaling and apoptosis regulators could represent a promising therapeutic approach for overcoming GBM treatment resistance. In this review, we summarize recent advances in our understanding of the HIF-apoptosis axis in GBM and discuss potential therapeutic strategies that target this molecular crosstalk.

This upstream activity of ANGPTL4 in regulating the proinflammatory SASP depends on its upregulation following a hypoxia-like response and HIF2A activation, and its proteolytic processing by the FURIN proprotein convertase. Altogether these findings shed light on a two-step activation of ANGPTL4 by HIF2A and FURIN in senescent cells and its upstream role in promoting the proinflammatory SASP, cancer and potentially other senescence-associated diseases.

The method demonstrated successful clinical validation through analysis of plasma samples from rats, achieving excellent correlation with reference LC-MS/MS methods while providing real-time therapeutic drug monitoring capabilities. This represents the first fluorometric approach for belzutifan quantification and establishes a new paradigm for anticancer drug monitoring that combines the advantages of carbon dot nanotechnology with clinically relevant near-infrared detection, offering significant potential for point-of-care therapeutic drug monitoring in oncology practice.

Early clinical experience with [¹⁷⁷Lu]Lu-PSMA radioligands and ongoing trials such as RENALUT and PRadR are exploring the feasibility of radioligand therapy targeting PSMA-positive ccRCC neovasculature. Although biological and kinetic barriers persist, PSMA-based imaging and therapy represent a feasible, rapidly translatable platform that bridges diagnosis and targeted treatment, marking a pivotal step towards personalised, imaging-guided management of advanced ccRCC.

Quisinostat also showed potent activity in leiomyosarcoma (LMS) cell lines (5.82-31.32 nM), which represent an additional complex karyotype soft tissue sarcoma. Quisinostat demonstrated strong preclinical activity and synergy with standard-of-care doxorubicin in models of UPS and LMS.

Radiopharmaceuticals such as 131I-MIBG and 177Lu-DOTATATE continue to play a pivotal role, achieving disease control in many patients. Cytotoxic regimens, particularly temozolomide, remain relevant, with some studies suggesting that SDHB-mutated PPGLs demonstrate a heightened sensitivity associated with MGMT promoter hypermethylation and reduced MGMT expression. Targeted agents are increasingly important: multi-kinase inhibitors such as sunitinib, anlotinib, and cabozantinib have shown meaningful activity. The landmark approval of belzutifan, a HIF-2α inhibitor, in 2025 represents the first oral targeted therapy for advanced/metastatic PPGL, which is particularly relevant for pseudohypoxic Cluster 1 tumors...This review summarizes current evidence and highlights ongoing clinical trials, underscoring a paradigm shift toward precision medicine and rational combination strategies. Collectively, these advances bring cautious optimism that metastatic PPGLs may soon become a more manageable chronic disease with improved survival and quality of life.

Novel approaches such as single-cell and spatial transcriptomics, organoid co-culture systems, and TME-derived biomarkers offer new opportunities for patient stratification and therapeutic development. Integrating TME biology into clinical practice is essential to overcome resistance and improve outcomes in urologic oncology.

Relative standard deviations (RSD) were below 2%, indicating precision and reproducibility. Owing to its simplicity and efficiency, the method is suitable for routine quality control in pharmaceutical laboratories.

Iron deficiency impairs skeletal muscle regeneration by stabilizing HIF-2α in MuSC, inducing Rb1 RNA expression, and repressing E2F-dependent proliferation. Transient HIF-2α inhibition rescues MuSC proliferation and muscle repair under iron-deficient conditions, highlighting HIF-2α as a potential therapeutic target to counteract sarcopenia in aging and chronic diseases.