Renal Cell Carcinoma

P2, N=30, Recruiting, Yale University | Trial completion date: Apr 2027 --> Apr 2028 | Trial primary completion date: Oct 2025 --> Jan 2027

Early clinical experience with [¹⁷⁷Lu]Lu-PSMA radioligands and ongoing trials such as RENALUT and PRadR are exploring the feasibility of radioligand therapy targeting PSMA-positive ccRCC neovasculature. Although biological and kinetic barriers persist, PSMA-based imaging and therapy represent a feasible, rapidly translatable platform that bridges diagnosis and targeted treatment, marking a pivotal step towards personalised, imaging-guided management of advanced ccRCC.

Recent trials demonstrate encouraging outcomes with ADC such as Enfortumab Vedotin (EV), Sacituzumab Govitecan (SG), Trastuzumab Deruxtecan (T-DXd), and Disitamab Vedotin (DV) in UC, improving response rates and Progression-Free Survival (PFS). In RCC, ADC against ENPP3, CD70, and TIM-1 show durable responses in early trials, though challenges such as dose-limiting toxicities require further investigation. Overall, this review underscores ADC as a transformative approach in uro-oncology, highlighting ongoing advancements in combination strategies and biomarker-driven applications to refine therapeutic outcomes and expand treatment options for these challenging malignancies.

Currently, molecular analyses guide treatment decisions in advanced cases following discussions in molecular tumour boards. Therefore, the classification of subtypes, together with their specific molecular alterations and signalling pathways, is gaining importance not only for targeted systemic therapy but also for the identification of patients with a hereditary tumour syndrome.The task of pathologists is to identify new tumour entities and genetically inherited tumour forms in order to ensure the best possible clinical care for patients.

Early detection and complete surgical resection are critical for a favorable outcome. The potential for metastasis and recurrence underscores the need for genetic testing (e.g., TSC gene mutations) and multidisciplinary collaboration to guide individualized treatment.

P2, N=15, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Nov 2026

P2, N=160, Completed, Merck Sharp & Dohme LLC | Active, not recruiting --> Completed

P2, N=10, Terminated, M.D. Anderson Cancer Center | Trial completion date: Jul 2027 --> Nov 2025 | Active, not recruiting --> Terminated | Trial primary completion date: Jul 2027 --> Nov 2025; The study met its prespecified futility criteria during the prespecified interim futility analysis after enrolling the first cohort of 10 patients.

This comprehensive analysis demonstrates the superior efficacy of ICI in younger aRCC patients across multiple cohorts, supporting the development of age-stratified therapeutic approaches. Age-dependent expression of TNFSF15 suggests potential molecular mechanisms underlying differential treatment responses.

Here, we synthesize insights from these approaches to define diverse CD8+ T-cell subsets and exhaustion trajectories, as well as the origins, phenotypic diversity, and functional states of other immune cells including tumor-associated macrophages, dendritic cells, natural killer cells and cancer-associated fibroblasts. Together, these findings highlight the transformative potential of single-cell technologies to unravel TME complexity, identify biomarkers of therapeutic response, and guide precision immunotherapy in RCC.

This study investigated the renoprotective action of linagliptin compared to doxorubicin against thioacetamide (TAA) and diethyl nitrosamine (DEN)-induced renocarcinogenesis in a rat model. These findings demonstrate that linagliptin, especially at 6 mg/kg/day, exhibits significant renoprotective activities through multifarious mechanisms involving antioxidant action and regulation of key molecular pathways. The present study presents evidence for the potential therapeutic application of linagliptin in renal manifestations of renocarcinogenesis.

Regarding therapeutic aspects, we discovered that DNA methyltransferase inhibitors serve as potential MAOB inducer in ccRCC. The current findings reveal novel mechanisms by which MAOB suppresses the malignancy of ccRCC and suggest that MAOB may serve as a valuable prognostic marker in the management of ccRCC.