Clear Cell Renal Cell Carcinoma

P=N/A, N=589, Completed, Mayo Clinic | Active, not recruiting --> Completed | Trial completion date: Jan 2027 --> Nov 2025 | Trial primary completion date: Jan 2027 --> Nov 2025

Overall, our findings show that casdatifan achieves meaningful, durable responses with manageable safety. These data establish a link between on-target HIF-2α pathway modulation, tumour biology and clinical efficacy.

Upregulated in ccRCC in a VHL-HIF2α-dependent manner, TRAIL is selectively essential in ccRCC cells, promoting cell proliferation by activating the p38 MAPK pathway and facilitating G1/S phase transition. Depletion of endogenous TRAIL or inhibition of HIF2α with belzutifan sensitizes ccRCC cell and tumor models to recombinant TRAIL, presenting a promising avenue for combination therapy in ccRCC.

We identified FDA-approved compounds acting through these pathways, three of which, Ribociclib, Ponatinib, and Dasatinib, showed superior efficacy to current therapies across renal cancer cell lines in preclinical screens. By acting through mechanisms distinct from current therapies, they represent promising candidates for combination strategies aimed at overcoming resistance and improving clinical outcomes in ccRCC.

This study demonstrates that downregulation of ALG6 induces ER stress-mediated apoptosis and enhances antitumor immunity by regulating PD-L1 expression in ccRCC. These findings suggest that ALG6 may serve as a potential therapeutic target for ccRCC.

These differences may reflect the limitations of body mass index as a biological indicator of obesity, together with variations in systemic inflammation, body composition, and treatment context. Here, we summarize current knowledge on obesity-driven immunometabolic rewiring in RCC and outline key priorities for the field, including obesity-relevant preclinical models, biomarkers of visceral adiposity and systemic inflammation, and clinical trials targeting immunometabolism.

This feasibility study demonstrates that ccRCC organoid generation from surgical specimens is achievable but remains limited by variable establishment rates and culture duration. Further optimization and integration of microenvironmental components will be necessary to enhance the translational relevance of this model.

Elevated miR34a levels may contribute to podocyte injury by inhibiting KLF4, thereby promoting the progression of obesity-related glomerulopathy. miR34a may also be related to the pathogenesis of ccRCC, especially in obese patients.

GSCA/GDSC-based drug sensitivity prediction suggested that high KIF7 expression was associated with increased predicted sensitivity to docetaxel and bleomycin, whereas no significant association was observed for I-BET-762. Additionally, it was associated with shaping the immune microenvironment. These findings highlight KIF7 as a potential prognostic biomarker and therapeutic target in ccRCC.

Awareness of such presentations is crucial, particularly in patients with a known history of ccRCC, as these lesions may clinically and radiologically mimic primary tumours of the affected sites. Careful evaluation of its histomorphological features and judicious use of immunohistochemical panels, together with clinical and radiological correlations, is the key to arriving at an accurate diagnosis.

AQP1 overexpression suppressed proliferation, migration, invasion, and xenograft growth, accompanied by upregulation of TNF-α, TNFRSF1A, Bax, and Cleaved Caspase-3 and reduced Vimentin, suggesting activation of TNF-related pro-apoptotic signaling. AQP1 is epigenetically silenced in ccRCC and suppresses tumor growth via TNF-mediated apoptosis, establishing it as an independent prognostic biomarker and candidate therapeutic target.

These findings represent computational predictions derived from transcriptomic and survival associations rather than direct evidence of therapeutic efficacy. The study provides a reproducible pan-cancer strategy for prioritizing candidate cancer types for future mechanistic and experimental validation of traditional Chinese medicine formulations.