Search Results (1,855)

Renal cell carcinoma (RCC) is a predominant malignancy of the urinary system, with clear cell renal cell carcinoma (ccRCC) representing 75–85% of clinical cases. Since the early stages are often asymptomatic, nearly 30% of patients present with metastases at diagnosis, which significantly complicates the prognosis. The diverse mechanisms and clinical indications of current strategies, despite recent breakthroughs in immunotherapy, pose a major challenge for systematic application. This review employs the cancer-immunity cycle as a framework to evaluate four critical steps: antigen presentation, T-cell activation, reversal of exhaustion, and immune evasion in the tumor microenvironment. We introduce the major immunotherapy strategies in RCC in this cycle and summarize their clinical position. Combining immune checkpoint inhibitors (ICIs) with tyrosine kinase inhibitors (TKI) has redefined the first-line standard for advanced RCC by addressing both T-cell infiltration barriers and functional suppression. Standalone approaches such as tumor vaccines and cytokines in contrast have shown limited efficacy in advanced settings. In this context, we further propose emerging research directions, such as individualized immunotherapy and multi-target blockade, and point out the relevant biomarkers, offering an integrated perspective of the RCC immune landscape and providing insights for both clinical practice and future research. Full article

Background/Objectives: Sarcomatoid or rhabdoid renal cell carcinoma (sRCC) represents an aggressive dedifferentiated phenotype of RCC associated with high metastatic potential. The histologic composition of metastatic lesions arising from clear cell RCC with sarcomatoid/rhabdoid differentiation (ccRCC/sRCC) and its relationship to the primary tumor remain incompletely characterized. Methods: We retrospectively reviewed patients undergoing nephrectomy for ccRCC/sRCC who had at least one resected metastatic lesion between 2013 and 2025 at a single institution. Primary and metastatic lesions were characterized by the percentage of clear cell versus sarcomatoid/rhabdoid histology. Associations between sarcomatoid/rhabdoid percentage in the primary tumor, metastatic histology, metastatic location, and overall survival were examined. Results: Twenty-six patients with 63 metastases were included. Metastatic histology demonstrated substantial heterogeneity, with 27 lesions (43%) showing pure clear cell histology, 21 (33%) mixed, and 15 (24%) pure sarcomatoid/rhabdoid. Some patients had multiple metastases with differing histology. Increasing sarcomatoid/rhabdoid percentage in the primary was associated with a higher likelihood of sarcomatoid/rhabdoid in metastases (p < 0.001). ROC analysis demonstrated primary tumor sarcomatoid/rhabdoid percentage predicted sarcomatoid/rhabdoid differentiation in metastases (AUC 0.84, 95% CI 0.73–0.95). An optimal cutoff of 10% sarcomatoid/rhabdoid differentiation predicted sarcomatoid/rhabdoid features in metastases. Metastatic histology varied by site, with lymph node metastases more frequently demonstrating clear cell morphology and visceral metastases more commonly exhibiting sarcomatoid/rhabdoid features. Conclusions: Metastases arising from ccRCC with sarcomatoid/rhabdoid differentiation exhibit marked histologic heterogeneity. These findings highlight the complex biology of ccRCC/sRCC metastasis and underscore the need for studies examining molecular drivers of metastatic heterogeneity, as well as the relationship between metastatic histology and therapeutic response. Full article

Clear cell renal cell carcinoma (ccRCC) is driven by von Hippel-Lindau (VHL) tumor suppressor loss and persistent activation of hypoxia-inducible factors (HIFs), which coordinately regulate angiogenesis, metabolic reprogramming, redox balance, and tumor–immune interactions. Although immune checkpoint inhibitors and vascular endothelial growth factor-targeted therapies have improved outcomes, resistance remains common due to adaptive network plasticity. Selected natural products have been reported to exhibit multitarget regulatory activities that may influence interconnected oncogenic pathways. This review highlights how compounds such as curcumin, resveratrol, quercetin, and epigallocatechin-3-gallate modulate the VHL-HIF axis, disrupt metabolic and redox homeostasis, and influence tumor–immune system interactions in ccRCC. We propose a system-level framework in which natural products enhance therapeutic sensitivity; however, further validation is required for clinical translation. Full article

Objective: Solitary kidney tumors are a challenging scenario necessitating both oncologic efficacy and renal function preservation. Partial nephrectomy (PN), when feasible, remains the gold standard for management. We examine intraoperative techniques and their association with renal function decline in patients with solitary kidneys undergoing PN. Methods: In two high volume academic referral centers, we analyzed patients that underwent PN in a solitary kidney from 2000 to 2023. Patient characteristics, tumor details, and operative details were obtained. Chronic kidney disease (CKD) upstaging from pre- to postoperative was the primary outcome, with multivariable analysis examining the association between intraoperative factors and CKD progression. Results: In total, 104 patients were included, of which 38 (36.5%) experienced CKD upstaging. Mean eGFR decline was 15.4% at median follow-up of 16 months. Cold ischemia was associated with higher odds of CKD upstaging compared to warm ischemia (OR 3.64; 95% CI 1.06–12.52) and no ischemia (4.55; 95% CI 1.09). Notably, cold ischemia cases tended to involve significantly larger, more complex tumors in patients with lower baseline renal function. Ischemia time, parenchyma resection, renal volume change, operative time, and renorrhaphy type were not predictors of CKD upstaging. Conclusions: PN in solitary kidneys remains standard with evidence of excellent renal preservation in this cohort. Worse outcomes were observed with cold ischemia, although this more likely represents underlying tumor complexity with other uncontrollable factors; however, this should be explored further. These findings suggest that renal functional outcomes are likely reasonable in patients with solitary kidneys undergoing PN when appropriate patient selection and sound surgical technique are utilized. Full article

Background: Robot-assisted partial nephrectomy (RAPN) is an established nephron-sparing technique for localized renal tumors. It is performed using on-clamp (temporary renal artery clamping) or off-clamp (without hilar clamping) strategies. Comparative real-world evidence remains limited and is often confounded by non-randomized treatment allocation. Methods: This retrospective single-center study included 146 consecutive patients undergoing RAPN between 2020 and 2025. Patients were allocated to on-clamp (n = 108) or off-clamp (n = 38) groups based on tumor characteristics and intraoperative surgeon judgment. Perioperative, functional, and early oncological outcomes were analyzed. Tumor complexity was assessed using the RENAL nephrometry score. Surgical quality was evaluated using the Trifecta outcome (negative margins, warm ischemia time ≤25 min, and absence of Clavien–Dindo ≥III complications). Results: Off-clamp RAPN was more frequently applied in smaller tumors (p = 0.008), while RENAL scores were comparable between groups. Estimated blood loss was higher in the off-clamp group (260 ± 62 vs. 110 ± 35 mL; p < 0.0001), whereas transfusion rates and overall complication rates did not differ significantly. Trifecta achievement was similar between on-clamp and off-clamp RAPN (91.0% vs. 96.8%; p = 0.45). No significant differences were observed in early postoperative renal function (creatinine, hemoglobin, eGFR) or positive surgical margin rates. Conclusions: In this retrospective cohort, both on-clamp and off-clamp RAPN demonstrated comparable perioperative safety, functional outcomes, and early oncological efficacy. Differences in baseline tumor characteristics reflect selection bias rather than treatment effect. These findings support the feasibility of both techniques in appropriately selected patients, while highlighting the need for prospective comparative studies with adjustment for confounding factors. Full article

Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, demonstrates robust efficacy in glycemic control and weight reduction. However, substantial interindividual variability in treatment response is observed in clinical practice. In this narrative review, we summarize current evidence on clinical, genetic, and molecular predictors of tirzepatide response and discuss their implications for a precision medicine framework. Data from pivotal clinical trials, post hoc analyses, and relevant preclinical and clinical studies were evaluated to identify determinants of glycemic and weight loss responses, as well as hepatic and renal protective effects. Key clinical predictors include tirzepatide dose, duration of diabetes, β-cell function, baseline glycated hemoglobin, sex, age, race, concomitant therapies, and early treatment response. Genetic factors implicated in treatment variability include variants in GLP-1 receptor, GIP receptor, β-arrestin 1, transcription factor 7-like 2, fat mass and obesity-associated protein, and melanocortin 4 receptor, although tirzepatide-specific validation remains limited. Molecular biomarkers such as branched-chain amino acids, insulin-like growth factor–binding protein-1 and -2, the adiponectin-to-leptin ratio, high-sensitivity C-reactive protein, and interleukin-6 show potential as pharmacodynamic indicators of metabolic response. For organ-specific outcomes, procollagen type III N-terminal peptide and magnetic resonance imaging–proton density fat fraction are supported for assessing hepatoprotective effects, while cystatin C–based estimated glomerular filtration rate and urine albumin-to-creatinine ratio are validated markers of renoprotection. Additional candidates—including tumor necrosis factor receptor 1/2, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin—are promising but require prospective validation. Overall, predicting response to tirzepatide’s multifaceted therapeutic effects necessitates an integrated, multidimensional approach that incorporates clinical characteristics, genetic variation, and molecular profiling. Ongoing validation and harmonization of these predictors may help establish a precision medicine framework for optimizing tirzepatide therapy. Full article

Background/Objectives: Advanced renal cell carcinoma (aRCC) remains incurable, with no established optimal sequence of targeted therapies due to interpatient heterogeneity and acquired resistance. We developed a luciferase-enabled patient-derived orthotopic xenograft (PDOX) avatar platform to evaluate sequential targeted therapies in individualized aRCC models that recapitulate tumor architecture, proliferation, angiogenesis, metastasis, and PD-L1 expression. Methods: Tumor specimens from two renal cell carcinoma (RCC) patients were expanded subcutaneously in NOD/SCID mice, transduced with luciferase/red fluorescent protein (Luc/RFP), and orthotopically implanted into mouse kidneys (KiCa-Pt58: sarcomatoid RCC, pT3aN1M1, Fuhrman grade 4; KiCa-Pt118: clear cell RCC with sarcomatoid component, pT3aNxM0, Fuhrman grade 4, respectively). Tumor growth and metastasis were monitored weekly by bioluminescence imaging (BLI). Mice were randomized into vehicle control or four sequential treatment groups (Everolimus→Sunitinib [E→S], Sunitinib→Everolimus [S→E], Pazopanib→Sunitinib [P→S], Pazopanib→Everolimus [P→E]). Drugs were administered orally three times weekly until resistance (>200% BLI increase), with one switch. At necropsy, tumor burden, ex vivo BLI metastasis, weights, H&E histology, and immunohistochemistry (Ki67, CD44, CD31, PD-L1) were assessed. Results: Two independent experiments were performed. In dosing optimization, PDOX tumors recapitulated parental histology and proliferative indices, mirroring patient trajectories. KiCa-Pt58 (metastatic sarcomatoid RCC; deceased 1-month post-nephrectomy) showed aggressive features: rapid engraftment at low doses, early growth (week 2), and lung metastases in 78% of mice (sacrifice day 34), reflecting a fulminant course. KiCa-Pt118 (non-metastatic; patient recurrence-free >8 years post nephrectomy) exhibited indolent behavior: delayed engraftment requiring higher doses plus lymph node stromal (HK) support, slower growth (week 4), no metastases, and later sacrifice (day 78), consistent with remission. In sequential therapy evaluation, for KiCa-Pt58, P→E yielded greatest reductions in tumor weight (p < 0.01), lung metastases (p < 0.01), Ki67+ proliferation, CD31+ angiogenesis, and PD-L1 expression versus control; E→S and S→E were also effective. For KiCa-Pt118, S→E and P→E reduced tumor burden (p < 0.01) and Ki67⁺ proliferation; S→E lowered CD31 and PD-L1. Conclusions: This RCC PDOX platform faithfully preserves patient-specific biology—including metastatic propensity, engraftment efficiency, growth kinetics, and stromal dependency—while enabling real-time evaluation of sequential targeted therapies. Given the limited number of models tested, these findings provide proof-of-concept for individualized treatment exploration in advanced RCC and support future investigation of rational combinations with immune checkpoint blockade in humanized or immunocompetent systems. Full article

Tumor cell heterogeneity and multicellular interactions critically influence drug resistance, recurrence, and prognosis. Here, CPcellsubpopulation, a computational framework integrating scRNA-seq, bulk RNA-seq, and clinical data was developed to identify cancer progression-associated cell subpopulations. Then, the integrated analyses of scRNA-seq and spatial transcriptomics were performed to predict potential interactions, identify critical transcription factors, and predict candidate anticancer drugs. Across nine cancers, we detected cancer progression-associated cell subpopulations significantly linked to prognosis, with consistent patterns across cancer types. In renal cell carcinoma (RCC), we identified conserved metabolic^high UBE2C+ cancer cells linked to poor outcomes, metabolic reprogramming and low differentiation, and PLK1+ NK cells, plasma cells, and CDC20+ macrophages associated with advanced stages and unfavorable prognosis. Spatial mapping revealed spatial association of RCC progression-associated cancer and immune cell subpopulations, suggesting the potential role of the VEGF, GDF, PTN and IL16 pathways in the remodeling of the tumor microenvironment. Gene regulatory network analysis highlighted RAD21 as a key regulator linking metabolism and therapy resistance. This study provides a systematic pipeline to delineate cancer progression-associated cell subpopulations, uncovers metabolic^high UBE2C+ cancer cells as progression-associated tumor cell population, and nominates critical regulators and compounds as therapeutic targets. Full article

Background/Objectives: Boron neutron capture therapy (BNCT) relies on the selective delivery of boron-10 to tumor cells. Although 4-[¹⁰B]borono-L-phenylalanine (BPA) is currently the only clinically approved BNCT agent, it is limited by poor L-type amino acid transporter 1 (LAT1)/LAT2 selectivity and aqueous solubility. We previously developed 3-borono-5-fluoro-α-methyl-L-phenylalanine (5F-αMe-3BPA), a novel BPA derivative designed to be a LAT1-targeted BNCT/positron emission tomography theranostic agent. This study comprehensively characterizes its pharmacological profile and explores its pharmacokinetic optimization by modulating renal organic anion transporter 1 (OAT1). Methods: Transport kinetics of BPA, related analogs, and 5F-αMe-3BPA were analyzed in HEK293 cells stably expressing LAT1 or LAT2 using Michaelis–Menten analysis. Time-dependent cellular uptake and intracellular retention of BPA and 5F-αMe-3BPA were evaluated in T3M-4 pancreatic cancer cells with or without the LAT1 inhibitor JPH203. In vivo biodistribution was examined in T3M-4 tumor-bearing mice after intravenous administration of 5F-αMe-3BPA or BPA, with assessment of probenecid pretreatment. Results: 5F-αMe-3BPA retained LAT1 affinity comparable to that of BPA while showing markedly reduced LAT2-mediated transport, indicating improved LAT1/LAT2 selectivity. In T3M-4 cells, 5F-αMe-3BPA showed stronger LAT1 dependence, higher steady-state accumulation, and better intracellular retention than BPA under amino acid-containing conditions. Although 5F-αMe-3BPA achieved favorable tumor-to-plasma and tumor-to-muscle ratios in vivo, it was rapidly cleared from circulation. Probenecid pretreatment increased plasma exposure, reduced early renal accumulation, and significantly enhanced tumor boron accumulation, reaching approximately twofold higher levels than control. Conclusions: These findings establish 5F-αMe-3BPA as a highly LAT1-selective BNCT candidate and identify probenecid pretreatment as a clinically translatable pharmacokinetic strategy for maximizing therapeutic boron delivery. Full article

Background/Objectives: While ¹⁷⁷Lu-DOTATATE has demonstrated clinical efficacy in peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors (NETs), current dosing regimens do not account for potential sex-based pharmacokinetic differences. Our study systematically characterizes sex-dependent pharmacokinetic variations of ¹⁷⁷Lu-DOTATATE in preclinical models to provide the first preclinical evidence base informing future sex-stratified clinical investigations. Methods: Sex-stratified pharmacokinetic and biodistribution studies were conducted in male and female SD rats following intravenous administration of ¹⁷⁷Lu-DOTATATE at multiple dose levels: 2.86, 5.71, and 11.43 mCi/kg. Metabolic stability and renal excretion patterns were characterized. Safety assessments included acute toxicity, vascular irritation, hemolysis, and allergenicity testing. Therapeutic efficacy was evaluated exclusively in female AR42J xenograft-bearing CB-17 SCID mice. Results: Significant sex-dependent pharmacokinetic differences were observed at high (11.43 mCi/kg) and low (2.86 mCi/kg) dose levels, with females exhibiting 30–40% higher AUC and C_max values compared to males (p < 0.05). Both sexes demonstrated preferential accumulation in SSTR-expressing tissues, particularly the pancreas (females: 10.87 ± 2.51% ID/g; males: 9.10 ± 0.76% ID/g) and adrenal glands, with rapid clearance from non-target organs. Radio-HPLC analysis confirmed high metabolic stability with no detectable radiolabeled metabolites, and over 90% of radioactivity was recovered through renal excretion. Safety assessments demonstrated excellent tolerability across dose levels. In female xenograft models, treatment achieved tumor growth inhibition of 92.35–96.44% and 100% survival rate versus 10% in controls, though mid/high doses caused weight loss. Conclusions: Our study provides systematic preclinical evidence of sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, with females demonstrating significantly higher systemic exposure than males at specific dose levels. These findings establish the systematic preclinical evidence base for sex-dependent pharmacokinetic differences in ¹⁷⁷Lu-DOTATATE, providing a scientific rationale for incorporating sex as a stratification variable in future dosimetry-guided clinical studies. Full article

Objectives: To develop and rigorously evaluate a Hybrid Multi-Path Attention Convolutional Neural Network (HMPA-CNN) for the classification of kidney diseases across heterogeneous institutional datasets and imaging modalities. Materials and Methods: The proposed HMPA-CNN employs dual parallel pathways to disentangle spatial (3 × 3 convolutions) and textural (5 × 5 convolutions) representations, followed by attention-based feature recalibration and gated fusion. Performance was assessed on five geographically distinct datasets comprising 29,148 CT and MRI images collected from Turkey, Bangladesh, Jordan, Iraq, and publicly available international sources. The evaluation framework included three-class tumor discrimination, four-class renal pathology classification, six-class tumor subtyping, binary kidney stone detection, and chronic kidney disease (CKD) assessment under cross-modality conditions. Results: The model achieved 99.76% overall accuracy on the KidneyNeXt three-class dataset, 99.96% on the four-class multi-institutional CT dataset, and 99.74% on the independent Jordan cohort under a four-class configuration. In the more granular six-class tumor subtyping task, overall accuracy was 96.36%. The same architecture achieved 93.85% overall accuracy on the MRI-based CKD classification task, suggesting that the framework can be adapted to a different imaging modality. Across most classification tasks, specificity exceeded 99%, with benign–malignant misclassification remaining below 2%. Performance declined to 91.96% for kidney stone detection, reflecting the intrinsic difficulty of small-object localization in axial CT images. Conclusions: The dual-path architecture consistently preserved high discriminative performance across institutions, diagnostic granularities, and imaging modalities. Its stable specificity and low benign–malignant confusion suggest potential utility as a supportive tool within renal imaging workflows, particularly for screening and structured diagnostic assistance. Clinically, benign–malignant misclassification is the most critical error, as it may delay oncologic evaluation or lead to unnecessary follow-up. Therefore, the model should be used as a decision-support tool rather than an autonomous diagnostic system. Further prospective validation is required to determine its impact in routine clinical practice. Full article

Pulmonary nodules detected in patients with a history of malignancy are often clinically presumed to represent metastatic disease until proven otherwise. Granular cell tumor (GCT) is an uncommon, usually benign neoplasm of presumed Schwannian origin, which rarely occurs in the lung. Our aim is to emphasize the diagnostic challenges and the crucial role of histopathology in preventing overtreatment in oncology patients. Herein, we report the case of a 56-year-old woman with a previous history of papillary renal cell carcinoma diagnosed one year earlier, staged as pT1, WHO/ISUP grade 2, and treated with partial nephrectomy, with no evidence of residual disease or distant metastases at follow-up. During routine surveillance, she developed a solitary pulmonary nodule. Chest computed tomography (CT) showed a 12 mm solid nodule in the left upper lobe which was then further investigated with a positron emission tomography with 2-[¹⁸F] fluoro-2-deoxy-D-glucose [(¹⁸F)-FDG PET/CT, revealing a low glucidic uptake (SUVmax 4 and SUV mean 1.4). Endobronchial ultrasound-guided biopsy was non-diagnostic. Given the patient’s oncological history, the solid appearance on CT, and the mild FDG uptake, metastatic disease could not be excluded, and a parenchyma-sparing diagnostic wedge resection was performed. Histology showed a well-circumscribed proliferation of epithelioid cells with abundant granular eosinophilic cytoplasm and bland nuclei. Immunohistochemistry demonstrated diffuse S100 and CD68 positivity, supporting the diagnosis of primary pulmonary granular cell tumor. This case underscores the critical role of histopathological evaluation in the assessment of solitary pulmonary nodules, emphasizing that lesions identified during oncologic surveillance are not invariably indicative of malignancy. Full article

Background/Objectives: The rapid expansion of targeted therapies has reshaped oncology by exploiting ligand-receptor interactions (LRI) to improve treatment specificity and patient outcomes. However, the data describing these ligands remain fragmented across multiple sources, limiting accessibility for researchers and clinicians. To address this gap, we developed the OncoSolidDB, the first curated and oncology-focused bioinformatics database dedicated to ligands associated with solid malignancies. Methods: OncoSolidDB integrates and harmonizes data from reliable repositories, including ChEMBL, DrugBank and the Anti-Cancer Fund, consolidating curated structural, chemical, pharmacological, and clinical annotations along with standardized identifiers. Results: The database currently encompasses 243 ligands across 15 major solid tumor types including breast, lung, colorectal, melanoma, prostate, gastric, ovarian, cervical, bladder, esophageal, head and neck, thyroid, pancreatic, renal and liver cancer (Hepatocellular Carcinoma, HCC). Each entry is annotated by standardized identifiers (DrugBank, ChEMBL), approval year, chemical structures (SMILES strings, 2D images), and downloadable protein structure files (PDB format). Temporal coverage spans 1953–2025, enabling exploration of historical trends in oncology drug approvals. The database content is suitable for bioinformatics analysis, molecular docking, virtual screening, ligand-based modeling, and drug repurposing studies. Outputs are available through a freely accessible web interface that supports search browsing by cancer type. Conclusions: By consolidating oncology-specific ligand data into a single, structured platform, OncoSolidDB offers a valuable resource for advancing drug discovery, repurposing strategies, and the rational design of next-generation targeted therapies for solid tumors. OncoSolidDB is accessible via our Bioinformatics Research PortalEinstein. Full article

Spontaneous regression of metastatic renal cell carcinoma is a rare and incompletely understood phenomenon. We report the case of a 61-year-old man with biopsy-proven pulmonary metastases from clear cell renal cell carcinoma who experienced durable tumor regression without receiving any systemic therapy. The patient underwent cryoablation of a symptomatic iliac bone metastasis and discontinued methotrexate, previously prescribed for inflammatory polyarthritis. Serial imaging demonstrated initial slow progression followed by significant shrinkage of pulmonary and mediastinal lesions, leading to a sustained partial response according to RECIST 1.1 criteria. No disease progression has been observed after extended follow-up. Two non-mutually exclusive mechanisms may explain this observation: restoration of antitumor immunity following withdrawal of immunosuppressive therapy, and a systemic immune response triggered by local tumor destruction (abscopal effect). Although such events are exceptional, this case highlights the potential interplay between immune modulation and local therapies in renal cell carcinoma. Further investigation is warranted to better understand these mechanisms and their potential therapeutic implications. Full article

Background/Objectives: To evaluate the clinical utility and diagnostic performance of quantitative MRI parameters (T1, T2*, R2*, and ADC) in differentiating renal tumor subtypes and WHO grades, and to assess their potential role in non-invasive tumor characterization. Methods: This retrospective study included 82 patients with histopathologically confirmed renal tumors who underwent preoperative contrast-enhanced MRI between July 2019 and January 2024. Quantitative measurements were obtained from tumor regions and contralateral healthy renal cortex using standardized ROI-based analysis. Parameters included T2*, native and post-contrast T1, R2* (1/T2*), and ADC values. Interobserver agreement was assessed. A Random Forest model was used as a supplementary analytical tool. Results: The cohort included 82 patients (mean age: 59.3 years). Tumors were classified into multiple subtypes, with clear cell carcinoma being the most common (n = 46). High-grade tumors (WHO grades 3–4) demonstrated significantly lower ADC values (p = 0.029) and larger tumor size (p = 0.0017). Significant differences in T2*, R2*, and ADC values were observed across tumor subtypes (p < 0.05). Quantitative MRI parameters demonstrated moderate discriminatory performance, with ADC emerging as the most robust biomarker. The Random Forest model achieved an overall accuracy of 93.2%, primarily driven by ADC and post-contrast T1 values. Conclusions: Quantitative MRI parameters, particularly ADC, provide clinically meaningful non-invasive biomarkers for renal tumor characterization. Their combined interpretation, supported by contralateral renal cortex comparison, may enhance clinical decision-making. Further validation in larger cohorts is warranted. Full article