Renal Cell Carcinoma

Exploratory genomic profiling revealed candidate, hypothesis-generating correlates of resistance (lower VHL and PBRM1; higher TSC2 and MSH3 alterations). By linking real-world outcomes with national genomic data, this study establishes a foundation for early identification and biomarker-guided management of PRD.

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.

Spatial transcriptomics identified immunosuppressive niches in a treatment-resistant lesion and immune checkpoint blockade synergized with GCAR1 in a xenograft model. Altogether, our data provide a proof of concept for treating GPNMB-expressing solid tumors with GCAR1 and more broadly targeting surface antigens driven by oncogenic gene fusions with CAR T cell therapies.

Treatment with pembrolizumab-belzutifan led to significantly higher disease-free survival, with a greater risk of grade 3 or higher toxic effects, than treatment with pembrolizumab monotherapy after nephrectomy in participants with clear-cell renal-cell carcinoma at increased risk for recurrence. (Funded by Merck Sharp and Dohme, a subsidiary of Merck [Rahway, NJ]; LITESPARK-022 ClinicalTrials.gov number, NCT05239728.).

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.

P2, N=30, Active, not recruiting, Dana-Farber Cancer Institute | N=45 --> 30

P=N/A, N=5, Not yet recruiting, Case Comprehensive Cancer Center | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

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.

A paired Bayesian strategy, graded priors for efficacy and no-borrowing priors for safety, produced transparent posterior probability summaries for the Japanese subgroup. This framework illustrates how borrowing can narrow uncertainty when exchangeability is plausible, while clarifying toxicity domains that may warrant closer monitoring, using published trial data.

Managing ALK-RCC is challenging due to its rarity and limited treatment options. Targeted therapies directed at the ALK gene may have a role in patients with ALK-RCC.

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.