Clear Cell Renal Cell Carcinoma

In contrast, under standard low-Cu conditions, CTR1 remains required for cellular Cu uptake and CuCOX metallation. Together, these findings define context-dependent Cu trafficking pathways in renal cancer and establish SEC-ICP-MS as a sensitive platform for assessing CuCOX metallation and mitochondrial metabolism, with potential applications in biomarker discovery and therapeutic targeting in RCC.

Third, we perform a cistrome-wide association study in ccRCC, validating five established RCC risk loci and identifying six novel loci, including a locus at 12q24 linked to SCARB1 that was functionally validated. These datasets provide new perspectives on the role of developmental pathways in ccRCC tumorigenesis, insights into epigenetic mechanisms of ccRCC heritability, and a comprehensive epigenomic atlas for the research community.

ATP1A1 emerges as a potential therapeutic target, with functional implications in angiogenesis and immune modulation. These findings highlight the clinical relevance of the identified gene signatures and support the development of personalized treatment strategies for ccRCC patients.

Given the role of sex hormones in metabolic regulation, we examined the expression of estrogen (ER), androgen (AR), and progesterone (PR) receptors...The dedifferentiation and browning of adipocytes, altered adipocytokine expression, and increased lactate production observed in hRAN reflect the metabolic stress imposed by the tumor environment. Here, we provide evidence, using an ex vivo model, of a dynamic partnership between human adipose tissue and ccRCC tumors.

PTX3 and IL-6 are potential biomarkers of disease severity and prognosis. Targeting inflammaging pathways could offer new therapeutic strategies for RCC, particularly in aggressive disease forms.

P1, N=1314, Recruiting, Exelixis | Active, not recruiting --> Recruiting

Additionally, a cell-permeable peptide has been designed to disrupt the ternary complex and inhibit ccRCC progression in tumor cells and patient-derived xenografts. Thus, our findings not only provide new insights into the prominent role of PRAME in mediating C/EBPβ and EZH2 regulation of NTN4 and tumor metastasis, but also highlight a promising strategy for ccRCC therapy by targeting the C/EBPβ-PRAME-EZH2 complex.

Notably, targeting CDK13 with the small-molecule inhibitor 1NM-PP1 potentiates METTL16 depletion-mediated anticancer effects. Our findings establish a kinase-RNA modifier axis that links CDK13 to epitranscriptomic control of lipid metabolism, positioning the CDK13-METTL16-ACLY pathway as a promising target for precision therapies against ccRCC.

In conclusion, [68Ga]Ga-PCA is a bispecific PET tracer that targets both hypoxic tumor cells and tumor neovasculature by binding to both CAIX and PSMA. The probe exhibited significant specificity, advantageous imaging contrast, and robust blocking validation, indicating its potential for molecular imaging of malignancies, including clear cell renal cell carcinoma (ccRCC).

OAS3 is upregulated in ccRCC and promotes tumor progression by mediating the infiltration of immune cells in the TME. OAS3 represents a promising therapeutic target for enhancing the antitumor effects of immune checkpoint inhibitors.

P2, N=314, Recruiting, National Cancer Institute (NCI) | Trial completion date: Feb 2026 --> Feb 2027 | Trial primary completion date: Feb 2026 --> Feb 2027

pneumoniae suppressed S-nitrosylation of tripartite motif containing protein 28 (TRIM28) by diminishing Mn2+ levels, allowing TRIM28 to physically interact with the transcription factor SP1 to promote the transcription of solute carrier family 27 member 1 (SLC27A1) and lipid deposition. Taken together, these findings indicate that tumor-resident S. pneumoniae plays an important role in conferring pazopanib resistance, suggesting that S. pneumoniae could serve as a potential biomarker of pazopanib response in ccRCC.