Multicenter randomized trial of deferred cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma receiving checkpoint inhibitors: the NORDIC-SUN-Trial

BMC Cancer, Journal Year: 2024, Volume and Issue: 24(1)

Published: Feb. 24, 2024

Abstract Background Primary tumor removal by cytoreductive nephrectomy in synchronous metastatic renal cell carcinoma patients has been investigated the context of various treatment regimens. Two randomized controlled trials role and timing era targeted therapy demonstrated that upfront should no longer be performed when require systemic therapy. Superiority checkpoint immunotherapy agents led to a paradigm change from therapies immunotherapy-based first-line with primary disease; thus, deferred needs verified setting. Furthermore, need exists for personalizing choices individual patient avoid unnecessary overtreatment. Methods/design To explore impact this group receiving immunotherapy, we initiated randomized, trial comparing surgery. The integrates comprehensive translational research program specimen sampling biomarker analysis. Discussion aims show improves overall survival carcinoma, furthermore, identify relevant biomarkers personalized cancer management. Trial registration ClinicalTrials.gov NCT03977571 June 6, 2019.

Language: Английский

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Deciphering glutamine metabolism patterns for malignancy and tumor microenvironment in clear cell renal cell carcinoma

Clinical and Experimental Medicine, Journal Year: 2024, Volume and Issue: 24(1)

Published: July 6, 2024

Abstract Clear cell renal carcinoma (ccRCC) is the most common subtype of kidney cancer characterized by metabolic reprogramming. Glutamine metabolism pivotal in reprogramming, contributing to significant heterogeneity observed ccRCC. Consequently, developing prognostic markers associated with glutamine could enhance personalized treatment strategies for ccRCC patients. This study obtained RNA sequencing and clinical data from 763 cases sourced multiple databases. Consensus clustering 74 related genes (GMRGs)- profiles stratified patients into three clusters, each which exhibited distinct prognosis, tumor microenvironment, biological characteristics. Then, six (SMTNL2, MIOX, TMEM27, SLC16A12, HRH2, SAA1) were identified machine-learning algorithms develop a predictive signature metabolism, termed as GMRScore. The GMRScore showed differences expression profile immune checkpoints, abundance cells, immunotherapy response Besides, nomogram incorporating features strong performance prognosis ALDH18A1, one GRMGs, elevated level was markedly poorer integrated cohort, validated proteomic profiling 232 samples Fudan University Shanghai Cancer Center (FUSCC). Conducting western blotting, CCK-8, transwell, flow cytometry assays, we found knockdown ALDH18A1 significantly promoted apoptosis inhibited proliferation, invasion, epithelial-mesenchymal transition (EMT) two human lines (786-O 769-P). In conclusion, developed metabolism-related ccRCC, tightly linked microenvironment response, potentially facilitating precision therapy Additionally, this revealed key role promoting progression first time.

Language: Английский

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KIDNEY-PAGER: analysis of circulating tumor DNA as a biomarker in renal cancer – an observational trial. Study protocol

Acta Oncologica, Journal Year: 2024, Volume and Issue: 63, P. 51 - 55

Published: Feb. 23, 2024

Management of localized renal cell carcinoma (RCC) is challenged by inaccurate methods to assess the risk recurrence and deferred detection relapse residual disease after radical or partial nephrectomy. Circulating tumor DNA (ctDNA) has been proposed as a potential biomarker in RCC.

Language: Английский

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Lessons learned from spatial transcriptomic analyses in clear-cell renal cell carcinoma

Nature Reviews Urology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

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Early-Stage Renal Cell Carcinoma: Who Needs Adjuvant Therapy?

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 543 - 543

Published: Feb. 21, 2025

Surgery is the oldest modality of kidney cancer therapy and usually first step in treatment process. To improve surgical outcomes, adjuvant frequently administered to eliminate residual tumors reduce risk recurrence metastasis. However, not all patients require treatment. The decision regarding whether treat or renal cell carcinoma depends on recurrence, including tumor stage histology, clinical, biological, personal factors. This article will address challenges treating with review current evidence ongoing clinical trials.

Language: Английский

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RCC-Ma Loss Predicts Poor Survival and Metastatic Risk in Clear Cell Renal Cell Carcinoma

Pathology - Research and Practice, Journal Year: 2025, Volume and Issue: 269, P. 155919 - 155919

Published: March 20, 2025

With the increasing number of renal cell carcinoma subtypes and implications for prognosis therapy, correct classification masses remains a challenging issue. Clear (ccRCC) is tumor with an immunoprofile that often does not follow paradigmatic rules. Thus, aim this study was to analyze heterogeneity immunohistochemical staining patterns in ccRCC regarding patient prognosis. The cohort consisted 727 patients surgical treatment between 1995 2006 comprehensive clinicopathological information follow-up data. Only 1.6 % received modern targeted therapy after surgery. were stratified analogue Leibovich Risk Score (LRS). A tissue microarray immunohistochemically stained vimentin, CAIX, CD10, RCC-Ma, AMACR, CK7 CD117. expression semiquantitatively scored tested association features survival. Loss RCC-Ma independent prognostic biomarker disease specific survival (p = 0.01) associated higher risk developing metastasis intermediate group LRS as well aggressive features, such grade stage, necrosis. other analyzed biomarkers had no impact on As predictor poor metastatic risk, likely be valuable contributor stratification patients. Moreover, provides resource investigations natural, therapy-naive clinical course can serve reference collectives, including treated up-to-date therapies.

Language: Английский

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Mitochondrial miRNA miR-134-5p Play Oncogenic Role in Clear Cell Renal Cell Carcinoma

Biomolecules, Journal Year: 2025, Volume and Issue: 15(3), P. 445 - 445

Published: March 20, 2025

Mitochondrial miRNAs (mitomiRs), which are that located within mitochondria, have emerged as crucial regulators in a variety of human diseases, including multiple types cancers. However, the specific role mitomiRs clear cell renal carcinoma (ccRCC) remains elusive. In this study, we employed combination experimental and bioinformatic approaches to uncover diverse abundant subcellular distribution mitochondria ccRCC. Notably, RNA sequencing after mitochondrial fractionation identified miR-134-5p miRNA predominantly detected 786O cells, its expression is significantly upregulated compared 293T cells. Differential survival analyses from TCGA reveal upregulation prevalent closely associated with poor outcomes ccRCC patients. Functionally, exogenous overexpression mimics promotes migration both Caki-1 Mechanistically, overexpressing mimic dramatically downregulates mRNA levels CHST6, SFXN2, GRIK3, whereas inhibitor markedly upregulates their expression. these target mRNAs also The downregulated signatures GRIK3 correlated Taken together, our work identifies novel mitomiR, miR-134-5p, ccRCC, provides potential targets could serve effective biomarkers for diagnosis prognosis, opens new avenues understanding mitomiR-directed regulatory network progression.

Language: Английский

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Enhanced anti-tumor effects of combined electric fields, cabozantinib, and radiation therapy in metastatic renal cell carcinoma

Clinical & Translational Oncology, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

Language: Английский

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New Tissue Markers in Renal Neoplasms Using Absolute Quantitative Proteomics and the Total Protein Approach Normalised with Protein Deglycase Dj-7 (Park-7)

Published: Jan. 1, 2025

Language: Английский

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Prognostic value of systemic immune-inflammation index in patients with metastatic renal cell carcinoma treated with systemic therapy: a meta-analysis

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: June 19, 2024

Objective A novel systemic immune-inflammation index (SII), based on the neutrophils, lymphocytes, and platelet counts, is associated with prognosis of several cancers, including non-metastatic renal cell carcinoma (RCC). In present study, we evaluate prognostic significance SII in patients metastatic RCC (mRCC) treated therapy. Method Relevant studies were searched comprehensively from Web Science, PubMed, Embase Cochrane Library up to January 2024. The pooled hazard ratio (HR) 95% confidence interval (CI) extracted each study value mRCC tyrosine kinase inhibitor (TKI) or immune checkpoint (ICI). Results total 12 4,238 included final analysis. High was significantly correlated poor overall survival (OS, HR = 1.88; CI 1.60–2.21; P < 0.001) progression-free (PFS, 1.66; 1.39–1.99; 0.001). Stratified by therapy, high also related OS (TKI: 1.63, 0.001; ICI: 2.27, PFS 1.67, 1.88, 0.002). Conclusion conclusion, could serve as an unfavorable factor therapies, elevated worse prognosis. Whereas, more prospective large-scale are warranted validate our findings. Systematic review registration https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024522831 , identifier CRD42024522831.

Language: Английский

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