Renal Cell Carcinoma

This will help provide a definitive understanding of the safety and efficacy of dupilumab in patients with a history of cancer and inform clinical practice. In summary, although the initial findings are promising, comprehensive research is essential to ensure the optimal management of AD in patients with a history of malignancies.

Its significant upregulation in ccRCC tissues and association with poor prognosis underscore its potential as a prognostic biomarker for RCC. Understanding the regulatory interactions among LRRC75A‑AS1, miR‑370‑5p and ADAMTS5 may provide new insights into the molecular mechanisms underlying RCC and facilitate the identification of novel therapeutic targets.

P1, N=5, Completed, Inge Marie Svane | Unknown status --> Completed

P1, N=52, Active, not recruiting, Merck Sharp & Dohme LLC | Trial completion date: Jul 2025 --> Jul 2026 | Trial primary completion date: Jul 2025 --> Jul 2026

Overall, 73% (8/11) tumors with TSC2 IHC loss and underlying pathogenic alterations in TSC2 showed heterogeneous protein loss, with rare interspersed positively staining tumor cells. These data support TSC2 IHC as a potentially useful assay for the diagnostic workup of renal tumors suspected to belong to the TSC/mTOR-associated subgroups.

METTL1 associated with m7G may serve as a potential biomarker for ccRCC prognosis and diagnosis. Moreover, it may affect the prognosis of ccRCC by regulating the tumor immune microenvironment, providing a potential therapeutic target for immunotherapy. These results provide a new perspective on the role of M7G-related RNAs in ccRCC pathogenesis.

Noncellular therapies targeting CD70, such as antibody-drug conjugates, monoclonal antibodies, radionuclides, and cytokines, are currently under investigation, with early data showing encouraging results as well. Efforts are already underway to further improve and optimize CD70-based therapies.

P2, N=10, Not yet recruiting, Memorial Sloan Kettering Cancer Center

Nemvaleukin was well tolerated and demonstrated promising antitumor activity across heavily pretreated advanced solid tumors. Phase 2/3 studies of nemvaleukin are ongoing.

High CD64 expression was also correlated with increased serum CRP levels. The CRP-CD64 signal was linked to the protumor activation of TAMs and could be a promising target for anticancer immunotherapy in ccRCC.

Among the alterations discussed, we focused on the ones that could be treated with already available drugs, such as MET-driven papillary RCC, mechanistic target of rapamycin altered chromophobe RCC, anaplastic lymphoma kinase-rearranged RCC, and fumarate-hydratase deficient RCC. Furthermore, we focused on the currently ongoing clinical trials and further evidence for all the other entities, such as SMARCB1-deficient RCC, TFE3 and transcription factorEB (TFEB)-altered RCC, and Elongin C (ELOC)-mutated RCC. The vast heterogeneity of nccRCC does not allow a one-size-fits-all solution; therefore, molecular characterization is the path toward effective therapies and fully personalized medicine for these entities.

P1, N=278, Active, not recruiting, MacroGenics | Recruiting --> Active, not recruiting | Trial completion date: Mar 2026 --> Jun 2025

Chitosan-gold nanoparticles conjugated with Lapatinib significantly reduced LINC01615 expression in lung cancer cell lines while enhancing apoptosis rates. Therefore, these nanoparticles could be considered a promising therapeutic candidate for treating cancers with overexpression of LINC01615.

Our case set highlights the diagnostic challenges of molecularly defined renal tumors and expands the morphological spectrum of SDH-deficient RCC with unusual histological features. Clinically, these tumors appear to be aggressive.

This activity correlated with intra-tumoral enrichment and clonal expansion of effector CD8+ T cells, decreased regulatory T cell levels, and enrichment of pro-inflammatory, anti-tumor myeloid cell populations. Our findings support further clinical investigation of the combination of DR-18 and anti-CTLA-4 in RCC.

The current study suggests that B7-H3 CAR-T cells exhibit significant efficacy in targeting and eliminating RCC cells, indicating a promising cellular immunotherapy approach for RCC treatment.

P1, N=325, Active, not recruiting, Exelixis | Trial completion date: Nov 2024 --> May 2027 | Trial primary completion date: Nov 2024 --> Aug 2026

P2, N=26, Completed, Centre Leon Berard | Recruiting --> Completed | N=77 --> 26 | Trial primary completion date: Nov 2023 --> Oct 2024

No tumor recurrence was observed during the follow-up of almost 16 months. FH-RCC patients with liver metastasis can achieve a good prognosis through early resection of primary tumor and metastatic lesions combined with targeted therapy.

The quality-of-life scores of patients in the Retroperitoneal group were higher (P0.05). Compared with the transperitoneal approach, the retroperitoneal method of RAPN is equally safe and is associated with improved perioperative status, lower stress response, and better quality of life for RCC patients.

Finally, analysis of immune signatures and clinical characteristics implied that, the activity of the innate immune, diagnostic age, clinical stage, Tumor-Node-Metastasis (TNM) stage and immune types, might play specific roles in modulating tumor prognosis. The study demonstrated that YTH family genes had the potential to predict tumor prognosis, in which the YTHScore illustrated equal ability to predict tumor prognosis compared to RWEScore, thus providing insights into prognostic biomarkers and therapeutic targets at the pan-cancer level.

Both human iPSC lines displayed normal morphology, expressed markers associated with stemness and differentiated into the three germ layers. The iPSC lines could be used as a disease-specific cellular model to understand furtherthe inherited disorder of Type 1 von Hippel-Lindau (VHL) disease.

Additionally, in vitro findings indicated that reduced expression of NSUN5 enhanced tumor cell senescence and simultaneously inhibiting cell proliferation and migration. These observations suggest that elevated NSUN5 expression is linked to poorer overall survival (OS) and progression-free survival (PFS), positioning NSUN5 as a viable diagnostic and prognostic biomarker in ccRCC.

P=N/A, N=694, Recruiting, University Hospital, Grenoble | Not yet recruiting --> Recruiting

The immune checkpoint inhibitor (CPI) pembrolizumab demonstrated a significant increase in disease-free and overall survival after surgery for the first time...Prospective biomarkers are currently not available. Here, kidney injury molecule‑1 (KIM-1) represents an initial promising biomarker in the prediction of adjuvant immunotherapy.

The patient exhibited normal glucose tolerance, consecutively passing an oral glucose tolerance test for 2 years. This case highlights the potential of lifestyle modifications in managing T2D in patients with a history of nephrectomy.

This study employed selective elimination analysis to identify candidate genes involved in the regulation of lambing trait in Hotan sheep. By investigating the molecular mechanisms underlying lambing rate in Hotan sheep, we developed molecular markers for twin lambing to enhance reproductive performance and promote the conservation and development of outstanding genetic resources in local Xinjiang sheep.

Molecular imaging aids in the non-invasive visualization and characterization of specific biomarkers such as carbonic anhydrase IX and CD70 within the tumours, which help to assess tumour heterogeneity and status. Target-specific molecular imaging of RCCs will substantially improve the diagnostic landscape of RCC and will further facilitate clinical decision-making regarding initial staging and re-staging, monitoring of recurrence and metastasis, patient stratification and selection, and the prediction and evaluation of treatment responses.

In conclusion, ICI-based combination therapy showed promising anti-tumor activity in SMARCB1-deficient medullary RCC patients. The presence of mature tertiary TLSs may partially elucidate the mechanism underlying treatment response.

Notably, overexpression of PLEKHA4 activated Wnt/β‑catenin signaling, reinforcing its role in promoting β‑catenin nuclear translocation and signaling activity. The present findings suggested that PLEKHA4 could serve as a potential therapeutic target for KIRC; inhibiting PLEKHA4 or modulating Wnt/β‑catenin signaling could provide new avenues for treatment strategies in KIRC.

Our results indicate that adenocarcinomas of intestinal-type, in distal vagina or vestibular vulva, might be a unique and single entity, probably originating from cloacogenic embryonic remnants and/or ectopic colorectal mucosae inclusions. An open question would be to explore the efficacy of systemic drugs prescribed in colorectal cancers, in VVAIts.

Notably, TFEB-rearranged RCCs concomitant with TFEB amplification/GCN gains tend to be aggressive, in contrast to the often indolent nature of TFEB-rearranged cases, irrespective of the extent of TFEB gene copy increase. Therefore, a TFEB FISH assay is essential for unclassified RCC cases that exhibit melanocytic marker expression, and fluorescent signals should be counted and interpreted acurrately.

Therefore, GATA3 could be useful as a panel of immunohistochemical stains that are used in diagnostic algorithm of vimentin-negative solid eosinophilic renal tumors. However, one should not solely rely on GATA3 as vimentin-negative solid eosinophilic renal tumors can have overlapping GATA3 expression.

PSMA-encoding FOLH1 gene expression correlates with neoangiogenesis and predicts PFS in m-ccRCC patients treated with sunitinib TKI, suggesting that PSMA PET could be explored as a noninvasive biomarker for guiding CST choice (IO/IO or IO/VEGFi) as well as prediction of treatment response to VEGFi in m-ccRCC patients.

Intricate signaling interactions between NK cells and various cellular subgroups were depicted and the developmental trajectory of NK cells was elucidated. A NK cells-related risk model was established, which can provide reliable prognostic information and identified patients with more probability of benefiting from therapy.

The underlying mechanisms associated with obesity in promoting the occurrence and development of kidney cancer mainly include: abnormal expression of adipocytokines, abnormal lipid metabolism, abnormalities in the insulin-like growth factor-I (IGF-I) axis and hyperinsulinemia/insulin resistance, hypoxia and inflammation. As adipose tissue is adjacent to the kidney, the effect of perirenal adipose tissue on the prognosis of kidney cancer is controversial, and some evidence supports the idea of the "obesity paradox".

Our results reveal that LTEMGs are closely associated with tumor microenvironment. Patients with high LTEMGs score might be resistant to immunotherapy.

The phase 3 clinical trial LITESPARK-005-belzutifan (HIF-2α inhibitor) demonstrated improvement in progression-free survival compared with everolimus in heavily pretreated patients unselected for somatic/germline VHL alterations (an objective response rate of 23% and a median time on therapy of 7.6 months in the belzutifan cohort), resulting in U.S. FDA approval for patients with advanced RCC. Both patients had an excellent clinical response (partial remissions ongoing at >12 and >20 months). Future studies should assess the merits of biomarker selection for belzutifan treatment.

All patients were alive at last follow up (median follow-up of 85 months). Our report is intended to raise awareness regarding rare instances of metastatic behavior for M/TSC-RCCfms.

H&E staining of major organs revealed no signs of damage, indicating the biosafety of St/siVEGFR-2@PCN-224@HA. The prepared St/siVEGFR-2@PCN-224@HA system enables triple inhibition of tumor growth via a combination of targeted therapy and genetic and photodynamic therapy to enhance the therapeutic effects on RCC.

CD70-targeted immuno-PET/CT imaging with [68Ga]Ga-NOTA-RCCB6 or [68Ga]Ga-NOTA-RCCB3 is a precise and superior method for evaluating tumor burden and suspected metastases in ccRCC patients. This advancement in imaging technology has the potential to improve the clinical decision-making process for this patient cohort significantly.

In summary, we conducted a comprehensive analysis of multi-omics data with 10 clustering algorithms to reveal the molecular characteristics of KIRC patients and validated the relevant conclusions by single-cell analysis and external data. Our findings discovered new KIRC subtypes and may further guide personalized and precision treatments.