Renal Cell Carcinoma

Compared to ccRCC, the plasma proteome of metastatic ChRCC is dominated by mitochondrial metabolic enzymes, revealing a systemic metabolic phenotype strikingly aligned with the known histologic accumulation of abnormal mitochondria in ChRCC cells.

Diagnostic advances including GPNMB immunohistochemistry, TRIM63 RNA in situ hybridization, and sequencing-based fusion panels improve detection of cryptic alterations. First-line ICI + VEGFR-TKI combinations are increasingly favored for metastatic tRCC in eligible patients, while optimal management of TFEB-amplified RCC remains uncertain.

This case highlights the rare occurrence of ccRCC with synchronous bladder metastasis and underscores the importance of comprehensive imaging, detailed morphologic and immunohistochemical evaluation, and a multidisciplinary approach. Robot-assisted cytoreductive surgery combined with modern systemic therapy represents an effective strategy for advanced ccRCC, emphasizing the need for individualized treatment and long-term follow-up in atypical metastatic scenarios.

A high gene expression was observed in lenvatinib non-responder cell lines, and DepMap dose-response curves indicated modest responses to VEGF inhibitors. In vitro, ACHN was more sensitive to VEGF inhibition, particularly cabozantinib, whereas G6PDi-1 had stronger effects in 786-O, impairing viability, migration, and clonogenic capacity. Our findings support G6PD as a biomarker of tumor aggressiveness and G6PDi-1 as a potential therapeutic in RCC models.

In 3D spheroids, resveratrol treatment was associated with reduced CIP2A protein levels and decreased fibronectin and α-SMA, consistent with attenuation of a mesenchymal marker profile. These proof-of-concept data link 6-day resveratrol exposure to CIP2A reduction and decreased mesenchymal marker expression in a human 3D RCC spheroid system; however, PP2A activity and downstream signaling, AMPK/SIRT1 activation, and EMT-relevant functional assays were not assessed, and validation across additional RCC models will be required.

Interestingly, A498-RAD10 cells were cross-resistant to cabozantinib, the tyrosine kinase inhibitor used in first-line treatment of mRCC with nivolumab...In silico data supported a context‑dependent role of PBRM1 in ccRCC patients. To the best of our knowledge, this is the first description of a mechanism of RAD001 and cabozantinib resistance through PBRM1 overexpression and CXCR7/CXCR4 downregulation and suggest new therapeutic perspective for cabozantinib-resistant patients.

Clinically, circIQGAP1 is overexpressed in RCC tissues and is correlated with poor outcomes. These findings revealed that circIQGAP1 promotes glycolysis-dependent RCC progression by stabilizing CARM1 to activate COL5A1, highlighting that this regulatory axis may provide an innovative strategy for RCC treatment.

We found a modest correlation between CD8 PET with [89Zr]Zr-berdoxam-crefmirlimab and intratumoral CD8 cell counts, likely because core needle biopsies do not fully represent the intratumoral heterogeneity of the CD8 cell distribution. Continued research is essential to evaluate in vivo CD8 PET signals, autoradiography, and CD8 T-cell presence by IHC in fully resected tumors. Further studies investigating the correlation between CD8 PET and immunotherapy outcomes are necessary to determine whether CD8 PET imaging could become a valuable tool for guiding immunotherapy development and informing clinical decision-making.

By profiling newborn and resident cells in intact microenvironments, it unveiled previously inaccessible interaction networks. SPTEdU-seq thus establishes a powerful framework for investigating cell fate dynamics in regeneration, development, and cancer.

This review also discusses how ECM composition and structure are altered in the tumor microenvironment (TME), thereby preventing cell interactions and promoting cancer growth. Finally, it compiles the existing studies to anticipate a future era in which MMPs could serve as effective prognostic biomarkers and potential treatment targets for RCC, with implications for improving diagnostic and therapeutic interventions targeting ECM remodeling to suppress cancer progression.

Mechanistically, VIP-mediated autophagy was associated with sirtuin 3 (SIRT3) downregulation and increased Ac-FOXO1 levels, with SIRT3 overexpression effectively counteracting the VIP-induced autophagic effects. Our findings demonstrate that VIP induces both cytotoxic effects and autophagy in VPAC1-expressing RCC cells through modulation of the SIRT3/FOXO1 signaling pathway, highlighting its potential therapeutic value for renal cell carcinoma.

P=N/A, N=174, Not yet recruiting, Sun Yat-sen University