On the translational front, HIF-2α inhibitors (such as belzutifan), strategies that suppress or oxidize lipids to trigger ferroptosis, and interventions targeting glutamine and one-carbon metabolism show promise when rationally combined with ICIs, TKIs, or anti-angiogenic therapies. We propose a stratified decision framework anchored in DCCD state, lipid-droplet/PLIN2 phenotype, ferroptosis sensitivity, and HIF activity, and discuss the emerging roles of radiopathomics (e.g., CT HU-PLIN2 coupling) and circulating metabolic fingerprints in companion diagnostics. Looking toward clinical deployment, advancing standardization within MSI/IBSI and FAIR data principles-and launching biomarker-enriched, prospective multicenter trials-will be essential to demonstrate the real-world value of precision metabolic oncology in the personalized treatment of ccRCC.

This approval, which is based on the results of the pivotal Phase 2 clinical trial MK-6482-004 (LITESPARK-004) 1,2,3 offers a therapeutic approach to managing certain VHL disease-associated tumours. This article describes the clinical data supporting belzutifan approval, in the EU, focusing on the VHL disease indication and its mechanism of action.

Although this molecular interaction may reflect SeMet-mediated attenuation of oxidative stress, biochemical data did not confirm changes in GSH/GSSG levels. These findings provide novel insights into the molecular mechanisms underlying MeHg neurotoxicity and its modulation by SeMet in fish brain, highlighting a potential protective role of organic Se against MeHg-induced molecular alterations.

P2, N=10, Recruiting, M.D. Anderson Cancer Center | Not yet recruiting --> Recruiting

Subgroup analysis showed higher efficacy of HIF-2α inhibitors (belzutifan) compared to VEGFR inhibitors (62% vs. 44%; 95% CI: 49-74 and 30-59, respectively)...Targeted therapy focusing on the molecular pathogenesis of VHL-associated RCC provides meaningful disease control while preserving renal function. HIF-2α inhibitors demonstrate superior efficacy and lower toxicity compared with VEGFR-targeted agents, representing a promising non-surgical alternative for managing VHL-related RCC.

P1, N=45, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Oct 2026 --> Jun 2027 | Trial primary completion date: Oct 2026 --> Jun 2027

This study systematically delineated a "microbiota-immunity-tumor" triangular knowledge framework that currently underpins the field, highlighting its maturation through bibliometric evidence. In the future, it is critical to integrate cross-scale mechanism exploration, standardized clinical translation pathways, and a global collaboration network to promote breakthroughs in personalized immunotherapy strategies, with direct relevance for clinical and perioperative care in oncology.

P3, N=904, Recruiting, Merck Sharp & Dohme LLC | Not yet recruiting --> Recruiting

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.

Consistent with these observations, two different allosteric HIF2 inhibitors, belzutifan and NKT2152, rapidly ameliorated hypercalcemia and cachexia in patients with ccRCC, including in some who did not exhibit objective tumor shrinkage. Our findings support prospective clinical studies to determine whether HIF2 inhibitors can be leveraged not only for tumor control, but also for the treatment of cancer-associated cachexia in renal cell carcinoma.

In treatment, radioligand therapy (PRRT) is used earlier in appropriate receptor-positive disease; cabozantinib improves progression-free survival after prior therapy; and belzutifan offers a biomarker-guided option for malignant pheochromocytoma/paraganglioma...We appraise strengths and limitations of key trials, note issues of access and toxicity, and highlight active areas in development (SSTR antagonists, alpha emitters, and dose-guided PRRT). Our goal is to provide a concise, evidence-based map of the field to support informed clinical judgment and future research priorities.

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.