{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:02:55Z","timestamp":1789642975858,"version":"4.0.0"},"reference-count":69,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Therapeutic options in renal cell carcinoma (RCC) have expanded rapidly, including adjuvant pembrolizumab, HIF-2\u03b1-directed therapy, and multiple effective first-line combinations for metastatic clear-cell RCC (ccRCC), yet treatment selection remains largely clinicopathologic. This review evaluates biomarkers at three clinical decision points: characterization of an indeterminate renal mass; recurrence-risk assessment and adjuvant treatment selection after nephrectomy; and first-line regimen selection in metastatic ccRCC. DNA-methylation classifiers and carbonic anhydrase IX-targeted [89Zr]Zr-girentuximab PET\/CT can improve characterization of selected renal tumors, but neither replaces histopathology in routine practice. After nephrectomy, elevated plasma kidney injury molecule-1 (KIM-1) and detectable circulating tumor DNA (ctDNA) identify patients at higher risk of recurrence; however, low tumor shedding limits ctDNA sensitivity, so a negative result does not exclude molecular residual disease or justify adjuvant de-escalation; neither biomarker is validated to direct surveillance, adjuvant therapy, or treatment escalation. In metastatic ccRCC, PD-L1 expression, tumor mutational burden, and individual genomic alterations do not reliably distinguish patients who should receive dual immune-checkpoint blockade from those who should receive an immune-checkpoint inhibitor plus a VEGFR tyrosine kinase inhibitor. Transcriptomic states, myeloid composition, and spatial immune organization provide more detailed treatment-relevant biology, but no prospective comparative trial has shown that biomarker-guided regimen selection improves outcomes. Clinical implementation will require standardized assays, independent multicenter validation, and prospective trials powered to test biomarker-by-treatment interactions.<\/jats:p>","DOI":"10.3390\/genes17091137","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T09:59:03Z","timestamp":1789639143000},"page":"1137","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarkers in Clear Cell Renal Cell Carcinoma: From Biological Association to Clinical Decision-Making"],"prefix":"10.3390","volume":"17","author":[{"given":"Hadi","family":"Al Etri","sequence":"first","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Al Zoghby","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-7568-517X","authenticated-orcid":false,"given":"Mohamad Sadek","family":"Zoghbi","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Karim","family":"Morad","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hatem","family":"Hassanein","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jad","family":"Chahoud","sequence":"additional","affiliation":[{"name":"Department of Genitourinary Oncology, Orlando Health Cancer Institute, Orlando, FL 32806, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"79","DOI":"10.14740\/wjon1279","article-title":"Epidemiology of Renal Cell Carcinoma","volume":"11","author":"Padala","year":"2020","journal-title":"World J. Oncol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/j.eururo.2022.08.019","article-title":"Epidemiology of Renal Cell Carcinoma: 2022 Update","volume":"82","author":"Bukavina","year":"2022","journal-title":"Eur. Urol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1001\/jama.2024.12848","article-title":"Renal Cell Carcinoma: A Review","volume":"332","author":"Rose","year":"2024","journal-title":"JAMA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1001\/jamaoncol.2021.4337","article-title":"Treatment Selection in First-Line Metastatic Renal Cell Carcinoma-The Contemporary Treatment Paradigm in the Age of Combination Therapy: A Review","volume":"8","author":"Navani","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1056\/NEJMoa2106391","article-title":"Adjuvant Pembrolizumab after Nephrectomy in Renal-Cell Carcinoma","volume":"385","author":"Choueiri","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1056\/NEJMoa2312695","article-title":"Overall Survival with Adjuvant Pembrolizumab in Renal-Cell Carcinoma","volume":"390","author":"Choueiri","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1056\/NEJMoa2313906","article-title":"Belzutifan versus Everolimus for Advanced Renal-Cell Carcinoma","volume":"391","author":"Choueiri","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1056\/NEJMoa2518245","article-title":"Adjuvant Pembrolizumab plus Belzutifan for Renal-Cell Carcinoma","volume":"395","author":"Choueiri","year":"2026","journal-title":"N. Engl. J. Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1038\/s41585-023-00818-y","article-title":"Diagnostic Liquid Biopsy Biomarkers in Renal Cell Cancer","volume":"21","author":"Zieren","year":"2024","journal-title":"Nat. Rev. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Kaba, A., Kanabur, P., Calais, J., Scott, A.M., Bernhard, J.-C., Mulders, P.C.R., \u00d6nal, B., Aksoy, T., Morris, M., and Master, V. (Eur. Urol., 2026). Performance of [89Zr]Girentuximab PET\/CT in Predicting the Presence of Any Renal Malignancy: A Reanalysis of the ZIRCON Trial, Eur. Urol., in press.","DOI":"10.1016\/j.eururo.2026.03.003"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1709","DOI":"10.1038\/s41388-024-03268-x","article-title":"A Urine DNA Methylation Assay for Early Detection of Renal Cancer","volume":"44","author":"Shi","year":"2025","journal-title":"Oncogene"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2691","DOI":"10.1200\/JCO.23.00699","article-title":"Plasma Kidney Injury Molecule-1 for Preoperative Prediction of Renal Cell Carcinoma Versus Benign Renal Masses, and Association with Clinical Outcomes","volume":"42","author":"Xu","year":"2024","journal-title":"J. Clin. Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1016\/j.annonc.2025.08.007","article-title":"Circulating Kidney Injury Molecule-1 (KIM-1) and Association with Outcome to Adjuvant Immunotherapy in Renal Cell Carcinoma","volume":"36","author":"Rini","year":"2025","journal-title":"Ann. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1016\/j.ccell.2022.11.001","article-title":"Mapping Single-Cell Transcriptomes in the Intra-Tumoral and Associated Territories of Kidney Cancer","volume":"40","author":"Li","year":"2022","journal-title":"Cancer Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1772","DOI":"10.1200\/JCO.21.01090","article-title":"External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer","volume":"40","author":"Oza","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/iju.70050","article-title":"Advances in Adjuvant Therapy for Renal Cell Carcinoma: Perspectives on Risk Stratification and Treatment Outcomes","volume":"32","author":"Furukawa","year":"2025","journal-title":"Int. J. Urol."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Carretero-Gonz\u00e1lez, A., Lora, D., Mart\u00edn Sobrino, I., S\u00e1ez Sanz, I., Bourlon, M.T., Anido Herranz, U., Mart\u00ednez Chanz\u00e1, N., Castellano, D., and de Velasco, G. (2020). The Value of PD-L1 Expression as Predictive Biomarker in Metastatic Renal Cell Carcinoma Patients: A Meta-Analysis of Randomized Clinical Trials. Cancers, 12.","DOI":"10.3390\/cancers12071945"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1016\/j.eururo.2023.04.003","article-title":"Current Landscape of Genomic Biomarkers in Clear Cell Renal Cell Carcinoma","volume":"84","author":"Cotta","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.eururo.2023.01.001","article-title":"Outcomes for International Metastatic Renal Cell Carcinoma Database Consortium Prognostic Groups in Contemporary First-Line Combination Therapies for Metastatic Renal Cell Carcinoma","volume":"84","author":"Ernst","year":"2023","journal-title":"Eur. Urol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"5794","DOI":"10.1200\/JCO.2008.21.4809","article-title":"Prognostic Factors for Overall Survival in Patients with Metastatic Renal Cell Carcinoma Treated with Vascular Endothelial Growth Factor-Targeted Agents: Results from a Large, Multicenter Study","volume":"27","author":"Heng","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1016\/S1470-2045(22)00128-0","article-title":"Nivolumab, Nivolumab-Ipilimumab, and VEGFR-Tyrosine Kinase Inhibitors as First-Line Treatment for Metastatic Clear-Cell Renal Cell Carcinoma (BIONIKK): A Biomarker-Driven, Open-Label, Non-Comparative, Randomised, Phase 2 Trial","volume":"23","author":"Vano","year":"2022","journal-title":"Lancet Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1038\/s41698-025-00912-x","article-title":"Enhanced Efficacy of Ipilimumab plus Nivolumab in Angiogenic Subtypes of Metastatic Clear-Cell Renal Cell Carcinoma","volume":"9","author":"Lu","year":"2025","journal-title":"npj Precis. Oncol."},{"key":"ref_23","first-page":"211","article-title":"The New WHO Category of \u201cMolecularly Defined Renal Carcinomas\u201d: Clinical and Diagnostic Features and Management Implications","volume":"42","author":"Kanakaraj","year":"2024","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Sanguedolce, F., Mazzucchelli, R., Falagario, U.G., Cormio, A., Zanelli, M., Palicelli, A., Zizzo, M., Eccher, A., Brunelli, M., and Galosi, A.B. (2024). Diagnostic Biomarkers in Renal Cell Tumors According to the Latest WHO Classification: A Focus on Selected New Entities. Cancers, 16.","DOI":"10.3390\/cancers16101856"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"100884","DOI":"10.1016\/j.modpat.2025.100884","article-title":"DNA Methylation-Based Classification of Kidney Neoplasms","volume":"38","author":"Singh","year":"2025","journal-title":"Mod. Pathol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/S1470-2045(24)00402-9","article-title":"[89Zr]Zr-Girentuximab for PET\u2013CT Imaging of Clear-Cell Renal Cell Carcinoma: A Prospective, Open-Label, Multicentre, Phase 3 Trial","volume":"25","author":"Shuch","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"eabn9828","DOI":"10.1126\/sciadv.abn9828","article-title":"Accurate Detection of Benign and Malignant Renal Tumor Subtypes with MethylBoostER: An Epigenetic Marker\u2013Driven Learning Framework","volume":"8","author":"Rossi","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1097\/JU.0000000000004912","article-title":"Cost-Effectiveness of Incorporating [89Zr]Zr-Girentuximab Positron Emission Tomography\u2013Computed Tomography for Characterizing Small Renal Masses","volume":"215","author":"Kanabur","year":"2026","journal-title":"J. Urol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1080\/14737140.2025.2454483","article-title":"Girentuximab Imaging in Renal Cancer: Diamond in the Rough or Just ZIRCON?","volume":"25","author":"Filippi","year":"2025","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1863","DOI":"10.2967\/jnumed.125.271332","article-title":"SNMMI\/EANM\/ACNM Procedure Standard\/Procedure Guideline on the Use of Molecular Imaging for Renal Mass Characterization","volume":"66","author":"Rowe","year":"2025","journal-title":"J. Nucl. Med."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1041","DOI":"10.1038\/s41591-020-0933-1","article-title":"Detection of Renal Cell Carcinoma Using Plasma and Urine Cell-Free DNA Methylomes","volume":"26","author":"Nuzzo","year":"2020","journal-title":"Nat. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105323","DOI":"10.1016\/j.esmoop.2025.105323","article-title":"Early Detection of Renal Cell Carcinoma: A Novel Cell-Free DNA Fragmentomics-Based Liquid Biopsy Assay","volume":"10","author":"Peng","year":"2025","journal-title":"ESMO Open"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Koumpis, P., Vartholomatos, E., Romeo, E., Alexiou, G.A., Argyropoulou, M.I., and Tsili, A.C. (2026). CT-Based Radiomics in the Characterization of Solid Renal Tumors: A Systematic Review. Cancers, 18.","DOI":"10.3390\/cancers18111758"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1425","DOI":"10.1038\/s41467-025-56784-z","article-title":"Artificial Intelligence Links CT Images to Pathologic Features and Survival Outcomes of Renal Masses","volume":"16","author":"Xiong","year":"2025","journal-title":"Nat. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Ivars, A., Pa\u00f1o, B., Puig, J., Fresno, M., Rodr\u00edguez, L., Sebastia, C., and Nicolau, C. (2026). The Central Role of Imaging in Renal Cell Carcinoma: A Comprehensive Review of Tumor Aggressiveness, Histology, and Radiomics. Cancers, 18.","DOI":"10.20944\/preprints202605.0012.v1"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1016\/S0140-6736(24)00917-6","article-title":"Renal Cell Carcinoma","volume":"404","author":"Young","year":"2024","journal-title":"Lancet"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1200\/JCO.19.00107","article-title":"Predicting Renal Cancer Recurrence: Defining Limitations of Existing Prognostic Models With Prospective Trial-Based Validation","volume":"37","author":"Correa","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1103","DOI":"10.1016\/S0140-6736(22)01658-0","article-title":"Adjuvant Atezolizumab versus Placebo for Patients with Renal Cell Carcinoma at Increased Risk of Recurrence Following Resection (IMmotion010): A Multicentre, Randomised, Double-Blind, Phase 3 Trial","volume":"400","author":"Pal","year":"2022","journal-title":"Lancet"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/S0140-6736(22)02574-0","article-title":"Adjuvant Nivolumab plus Ipilimumab versus Placebo for Localised Renal Cell Carcinoma after Nephrectomy (CheckMate 914): A Double-Blind, Randomised, Phase 3 Trial","volume":"401","author":"Motzer","year":"2023","journal-title":"Lancet"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1038","DOI":"10.1016\/S1470-2045(24)00211-0","article-title":"Perioperative Nivolumab versus Observation in Patients with Renal Cell Carcinoma Undergoing Nephrectomy (PROSPER ECOG-ACRIN EA8143): An Open-Label, Randomised, Phase 3 Study","volume":"25","author":"Allaf","year":"2024","journal-title":"Lancet Oncol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4510","DOI":"10.1200\/JCO.2025.43.16_suppl.4510","article-title":"Genomic Characterization of Baseline and Post-Progression Tumors in IMmotion010, a Randomized, Phase 3 Study of Adjuvant (Adj) Atezolizumab (Atezo) vs Placebo (Pbo) in Patients (Pts) with High-Risk Localized Renal Cell Carcinoma (RCC)","volume":"43","author":"Pal","year":"2025","journal-title":"J. Clin. Oncol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Xu, W., Rini, B.I., Albiges, L., Tang, X., Koeppen, H., Bex, A., Su\u00e1rez, C., Uzzo, R., Master, V., and Karam, J.A. (Eur. Urol., 2026). Comprehensive Genomic and Transcriptomic Characterization of Matched Primary and Recurrent Tumors in High-Risk Localized Renal Cell Carcinoma, Eur. Urol., in press.","DOI":"10.1016\/j.eururo.2026.03.023"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1080\/14737159.2026.2687507","article-title":"KIM-1 and beyond: Emerging Biomarkers for Adjuvant Immunotherapy in Clear Cell Renal Cell Carcinoma","volume":"26","author":"Rosellini","year":"2026","journal-title":"Expert Rev. Mol. Diagn."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3397","DOI":"10.1158\/1078-0432.CCR-21-0025","article-title":"Plasma KIM-1 Is Associated with Recurrence Risk after Nephrectomy for Localized Renal Cell Carcinoma: A Trial of the ECOG-ACRIN Research Group (E2805)","volume":"27","author":"Xu","year":"2021","journal-title":"Clin. Cancer Res."},{"key":"ref_45","first-page":"233","article-title":"Circulating KIM-1 and Survival Outcomes in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis","volume":"44","author":"Lu","year":"2026","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1080\/1354750X.2026.2664868","article-title":"Circulating KIM-1 as a Prognostic Biomarker and Predictor of Systemic Treatment Response in Renal Cell Carcinoma: A Systematic Review and Meta-Analysis","volume":"31","author":"Febriyanto","year":"2026","journal-title":"Biomarkers"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1111\/his.70047","article-title":"Recent Advances in Liquid Biopsy for Genitourinary Cancers: A Narrative Review","volume":"88","author":"Harrs","year":"2026","journal-title":"Histopathology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s13073-020-00723-8","article-title":"Comprehensive Characterization of Cell-Free Tumor DNA in Plasma and Urine of Patients with Renal Tumors","volume":"12","author":"Smith","year":"2020","journal-title":"Genome Med."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1093\/oncolo\/oyae180","article-title":"Association of Circulating Tumor DNA with Patient Prognosis in Surgically Resected Renal Cell Carcinoma","volume":"29","author":"Correa","year":"2024","journal-title":"Oncologist"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"4502","DOI":"10.1200\/JCO.2026.44.16_suppl.4502","article-title":"ctDNA Analysis in Participants with Renal Cell Carcinoma Treated with Adjuvant Pembrolizumab or Placebo in the KEYNOTE-564 Trial","volume":"44","author":"Choueiri","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1200\/JCO.2026.44.7_suppl.519","article-title":"Utility of Circulating Tumor DNA in Patients with Renal Cell Carcinoma at Increased Risk of Recurrence after Resection","volume":"44","author":"Lin","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1200\/JCO.2026.44.7_suppl.516","article-title":"Use of Ultra-Sensitive Whole Genome Circulating Tumor DNA Detection to Predict Early Recurrence in High-Risk Localized RCC after Nephrectomy: Preliminary Real-World Findings","volume":"44","author":"Zerey","year":"2026","journal-title":"J. Clin. Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e71019","DOI":"10.1111\/jcmm.71019","article-title":"Emerging Role of ctDNA Fragmentomics and Epigenetic Signatures in the Early Detection, Minimal Residual Disease Assessment, and Precision Monitoring of Renal Cell Carcinoma","volume":"30","author":"Kamli","year":"2026","journal-title":"J. Cell. Mol. Med."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"51","DOI":"10.2340\/1651-226X.2024.25581","article-title":"KIDNEY-PAGER: Analysis of Circulating Tumor DNA as a Biomarker in Renal Cancer\u2014An Observational Trial. Study Protocol","volume":"63","author":"Iisager","year":"2024","journal-title":"Acta Oncol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"500","DOI":"10.1158\/2159-8290.CD-18-0825","article-title":"Detection and Surveillance of Bladder Cancer Using Urine Tumor DNA","volume":"9","author":"Dudley","year":"2019","journal-title":"Cancer Discov."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Dermody, S.M., Bhambhani, C., Swiecicki, P.L., Brenner, J.C., and Tewari, M. (2022). Trans-Renal Cell-Free Tumor DNA for Urine-Based Liquid Biopsy of Cancer. Front. Genet., 13.","DOI":"10.3389\/fgene.2022.879108"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1016\/j.annonc.2026.02.017","article-title":"Nivolumab plus Ipilimumab versus Sunitinib for First-Line Treatment of Advanced Renal Cell Carcinoma: Final Analysis of Efficacy and Safety from the Phase III CheckMate 214 Trial","volume":"37","author":"Choueiri","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3475","DOI":"10.1038\/s41591-025-03867-5","article-title":"Pembrolizumab plus Axitinib versus Sunitinib for Advanced Clear Cell Renal Cell Carcinoma: 5-Year Survival and Biomarker Analyses of the Phase 3 KEYNOTE-426 Trial","volume":"31","author":"Rini","year":"2025","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/s41591-020-0839-y","article-title":"Interplay of Somatic Alterations and Immune Infiltration Modulates Response to PD-1 Blockade in Advanced Clear Cell Renal Cell Carcinoma","volume":"26","author":"Braun","year":"2020","journal-title":"Nat. Med."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"e2500416","DOI":"10.1200\/PO-25-00416","article-title":"Identification of Predictive Genomic Biomarkers in Metastatic Clear Cell Renal Cell Carcinoma: A Comprehensive Analysis of Real-World Clinicogenomic Data","volume":"10","author":"Rizzo","year":"2026","journal-title":"JCO Precis. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1001\/jamaoncol.2021.5981","article-title":"Final Overall Survival and Molecular Analysis in IMmotion151, a Phase 3 Trial Comparing Atezolizumab Plus Bevacizumab vs Sunitinib in Patients with Previously Untreated Metastatic Renal Cell Carcinoma","volume":"8","author":"Motzer","year":"2022","journal-title":"JAMA Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1038\/s41591-020-1044-8","article-title":"Avelumab plus Axitinib versus Sunitinib in Advanced Renal Cell Carcinoma: Biomarker Analysis of the Phase 3 JAVELIN Renal 101 Trial","volume":"26","author":"Motzer","year":"2020","journal-title":"Nat. Med."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"861","DOI":"10.1016\/j.annonc.2026.02.011","article-title":"Cabozantinib plus Nivolumab and Ipilimumab in Previously Untreated, Advanced Renal Cell Carcinoma: Final Results and Biomarker Analyses from the Phase III COSMIC-313 Study","volume":"37","author":"Motzer","year":"2026","journal-title":"Ann. Oncol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"3608","DOI":"10.1158\/1078-0432.CCR-26-0216","article-title":"Dissecting the Tumor Microenvironment to Identify Biomarkers of Outcome to Anti-PD-1 Therapy in Clear-Cell Renal Cell Carcinoma: Analyses of the HCRN GU16-260 Trial","volume":"32","author":"Paul","year":"2026","journal-title":"Clin. Cancer Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e012991","DOI":"10.1136\/jitc-2025-012991","article-title":"Spatial Transcriptomic Profiling of Metastatic Renal Cell Carcinoma Identifies Chemokine-Driven Macrophage and CD8+ T-Cell Interactions Predictive of Immunotherapy Response","volume":"13","author":"Kalogirou","year":"2025","journal-title":"J. Immunother. Cancer"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"119964","DOI":"10.1016\/j.cca.2024.119964","article-title":"Liquid Biopsy for Renal Cell Carcinoma","volume":"565","author":"Rajandram","year":"2025","journal-title":"Clin. Chim. Acta"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1038\/s41591-024-03141-0","article-title":"A Foundation Model for Clinical-Grade Computational Pathology and Rare Cancers Detection","volume":"30","author":"Vorontsov","year":"2024","journal-title":"Nat. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"e06165","DOI":"10.1002\/advs.202506165","article-title":"Radiomics-Based Unsupervised Clustering Identifies Subtypes Associated With Prognosis and Immune Microenvironment in Clear Cell Renal Cell Carcinoma: A Multicenter Study","volume":"12","author":"Guo","year":"2025","journal-title":"Adv. Sci."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"S1298","DOI":"10.1016\/j.annonc.2025.08.3207","article-title":"2591O Efficacy of Cabozantinib and Nivolumab in Cluster 1\/2 Metastatic Clear Cell Renal Cell Carcinoma: Results from OPTIC RCC, a Phase II Trial of a Novel RNAseq-Based Biomarker","volume":"36","author":"Haake","year":"2025","journal-title":"Ann. Oncol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1137\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T10:22:17Z","timestamp":1789640537000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/9\/1137"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,17]]},"references-count":69,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["genes17091137"],"URL":"https:\/\/doi.org\/10.3390\/genes17091137","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,17]]}}}