Carbonic anhydrase IX (CA-IX) is overexpressed in clear cell renal cell carcinoma (ccRCC) and hypoxic tumors, and is regarded as a potential target for tumor diagnosis and treatment. In this work, two ligands (HA and HFA) that contain HYNIC and benzenesulfonamide were designed and synthesized. Four 99mTc-labeled complexes with high labeling yields and good in vitro stability were obtained and evaluated. In the cell binding assay, the [99mTc]Tc-HA-TPPTS and [99mTc]Tc-HFA-TPPTS complexes showed higher targeting specificity and affinity for CA-IX than the other radiotracers. The micro-SPECT images and biodistribution results revealed that the [99mTc]Tc-HA-TPPTS complex had high tumor specific uptake and target-nontarget ratios at 60 min p.i. (tumor-to-blood ratio: 4.85 ± 0.09 and tumor-to-muscle ratio: 11.31 ± 1.37) and exhibited the ability to visualize tumors in nude mice bearing HT-29 tumors. Therefore, these results demonstrated that [99mTc]Tc-HA-TPPTS is a promising candidate probe targeting CA-IX for tumor imaging.

Gingerenone A inhibits LDHA-mediated glycolysis and restores sunitinib sensitivity in renal cell carcinoma.

Fibroblast activation protein (FAP) has been proposed as a pan-tumor target for PET imaging using FAP-targeted tracers. Here, we explore the potential value of FAP PET in renal tumors. Methods: Six patients with renal tumors (4 with clear cell renal cell carcinoma, 1 with papillary renal cell carcinoma, and 1 with renal oncocytoma) who were included in a prospective imaging study (NCT04147494) underwent [68Ga]Ga-FAPI-46 PET before nephrectomy. FAP PET radiotracer uptake and FAP expression by immunohistochemistry were assessed in the tumors and surrounding renal parenchyma. Results: Tumoral FAP radiotracer uptake was highest in clear cell renal cell carcinoma (median SUVmax, 3.1; range, 2.5-5.3), followed by renal oncocytoma (SUVmax, 1.9) and papillary renal cell carcinoma (SUVmax, 1.1). The FAP PET signal strongly correlated with FAP expression by immunohistochemistry (SUVmax; r = 0.93; P = 0.007). Conclusion: FAP expression in different renal tumors, including renal cell carcinoma, was lower when compared with cancers with known FAP expression, such as sarcoma. Although our data do not favor FAP-based theranostic approaches in renal cell carcinoma, studies in larger cohorts are warranted for conclusive evidence.

Response to letter to the editor: "Insights on nivolumab-based immunotherapy and prognostic stratification in older patients with metastatic renal cell carcinoma".

Novel tissue markers in renal neoplasms using molar-scale quantitative proteomics via the total protein approach normalised with protein deglycase DJ-1 (PARK7).

Node-RADS score on CT imaging predicts lymph node metastasis and survival in renal cell carcinoma: A multicenter diagnostic study.

Time-dependent changes in pathological risk factors of recurrence after renal cell carcinoma surgery.

Insights on nivolumab-based immunotherapy and prognostic stratification in older patients with metastatic renal cell carcinoma.

Comprehensive analysis and experimental confirmation identify ADRM1 plays an oncogenic and immunosuppression role in KIRC.

High lymphocyte infiltration and T cell exhaustion characterize the tumor microenvironment in renal cell carcinoma (RCC). Protein tyrosine phosphatase N22 (PTPN22), a protein tyrosine phosphatase that mediates proteins tyrosine dephosphorylation, is a negative regulator of T cell receptor signaling, but its role in tumor cells has been underappreciated. PTPN22 is highly expressed in RCC cells and positively correlated with PD-L1 protein expression. CBL was newly identified as a substrate of PTPN22, and our study reveals for the first time that CBL mediates the K48-linked ubiquitination of PD-L1. PTPN22 specifically interacts with CBL, catalyzing the dephosphorylation of tyrosine 700 and inhibiting CBL binding to PD-L1, thereby preventing CBL-mediated ubiquitination and degradation of PD-L1. This stabilization of PD-L1 promotes T cell exhaustion and immunosuppression. Through screening of traditional Chinese medicine monomers, we identified curcumin as a potential PTPN22 inhibitor. Curcumin reduces PTPN22 stability and PTPN22 expression by directly binding to PTPN22. In vivo experiments demonstrated that combining curcumin with immune checkpoint inhibition (ICIs) further promotes T cell activation, inhibits Tregs infiltration, and enhances ICIs efficacy against tumor growth. Therefore, PTPN22 represents a therapeutic target for improving T cell exhaustion in RCC and enhance ICIs efficacy through CBL-mediated ubiquitination and degradation of PD-L1.

Tissue architecture of cancer deviates from that of normal tissue and is closely linked to various features of cancer, including invasion and tumor immunity. However, pan-cancer analyses of cancer tissue architecture (CTA) remain limited. We applied non-negative matrix factorization to the expression data of 593 CTA-related genes from 28 cancer types in the Cancer Genome Atlas Project dataset, identifying seven distinct CTA signatures. A fibrous collagen-related signature, which is related to fibroblasts and the extracellular matrix, was relatively ubiquitous and represents a universal feature of cancer. In contrast, those associated with cell-cell adhesion or cell-stroma adhesion exhibited high tissue specificity. These findings were validated using Pan-Cancer Analysis of Whole Genomes data, spatial transcriptomics, and in vivo and in vitro models. In renal cell carcinoma, we found a strong correlation between network-forming collagen and patient survival, supported by mouse experiments showing that perturbation of this collagen promotes tumor growth. Additionally, several gene mutations and copy number alterations were found to correlate with changes in CTA. Our results suggest that CTA can be understood as a combination of components that influence the pathological features of cancer.

Renal cell carcinoma (RCC) is heterogeneous and frequently refractory to cytotoxic therapy. We investigated whether contexts with elevated DDR2—a collagenactivated receptor tyrosine kinase—are preferentially sensitive to regorafenib, a multikinase inhibitor with activity against DDR2. DDR2 mRNA was quantified by quantitative PCR in Caki1 (clear cell), ACHN (papillary), and Caki2 (papillary) relative to HK2. Shortterm viability was assessed by a tetrazolium (MTT) assay with fourparameter logistic fits to estimate the lowest observed effect concentration (LOEC) and halfmaximal inhibitory concentration (IC₅₀). In an ACHN xenograft model, mice were randomized to vehicle or regorafenib (10 mg/kg, intraperitoneally) every 3 days for 21 days. ACHN and Caki1 expressed higher DDR2 than HK2, whereas Caki2 was modest; ACHN xenografts retained elevation, whereas Caki2 xenografts did not. Regorafenib reduced ACHN viability with LOEC 1 μM and IC₅₀ 6.93 μM, while Caki2 first declined at 30 μM without reaching 50% inhibition. In vivo, regorafenib attenuated ACHN tumor growth with a significant difference by day 14. Clinically, higher DDR2 associated with inferior overall survival in The Cancer Genome Atlas papillary cohort (KIRP), with no consistent association in the clear cell cohort (KIRC). Across in vitro, in vivo, and in silico analyses, DDR2-high papillary contexts exhibit preferential regorafenib sensitivity, nominating DDR2-enriched papillary RCC for biomarker-guided repurposing and motivating protein-level and genetic validation.

Diagnostic challenges of aberrant TFE3 expression in renal cell carcinoma: A case report

Population-based utilization and survival of competing treatments for small renal masses: The growing role of thermal ablation.

Adrenal insufficiency is a recognized complication following adrenalectomy and, less commonly, nephrectomy due to the anatomical and functional relationship between the adrenal glands and kidneys. While unilateral adrenalectomy is typically well tolerated due to compensation by the contralateral adrenal gland, adrenal insufficiency may still occur, particularly in cases involving bilateral disease. Recognizing and managing this risk is critical in postoperative care to prevent life-threatening adrenal crises. We present a case of left renal cell carcinoma (RCC) with tumor thrombus (TT) level IV (extending into the right atrium). The surgery was completed exclusively through an abdominal approach without cardiopulmonary bypass (CPB). The surgical approach involved a left radical nephrectomy, left adrenalectomy, and removal of a large TT, which included a segment of the inferior vena cava (IVC) and the right adrenal vein. As a result, the right adrenal vein was sacrificed, and adrenal insufficiency was expected due to ligation of the right adrenal vein and removal of the left adrenal gland. However, one year after the procedure, adrenal insufficiency was not seen, perhaps due to venous collaterals draining the right adrenal gland. This case highlights that in the case of complete obstruction of the IVC by the TT of an RCC, the remaining adrenal vein can be sacrificed without causing adrenal insufficiency, perhaps due to the presence of multiple venous collaterals that developed from chronic obstruction of the IVC.

Immunotherapy-based treatment in renal collecting duct carcinoma: A retrospective case series analysis.

Final analysis of nivolumab plus cabozantinib for advanced renal cell carcinoma from the randomized phase III CheckMate 9ER trial.

Image-Guided Thermal Ablation of Upper Pole Renal Lesions ≤4 cm: Safety and Effectiveness.

Background: Systemic inflammation and nutritional status are key determinants of prognosis in metastatic clear-cell renal carcinoma (mccRCC). Composite indices such as the Systemic Immune–Inflammation Index (SII) and the Modified Glasgow Prognostic Score (mGPS) have demonstrated prognostic relevance across cancers, but real-world data in mccRCC remain limited. Methods: This retrospective, single-center cohort included patients with histologically confirmed mccRCC who received first-line tyrosine kinase inhibitor (TKI) monotherapy (sunitinib, pazopanib, or cabozantinib) between November 2022 and November 2024 at Etlik City Hospital (Ankara, Türkiye). Associations between inflammatory–nutritional indices (SII, mGPS) and progression-free survival (PFS) were evaluated using Kaplan–Meier and multivariable logistic regression analyses. Results: A total of 55 patients met eligibility criteria and were included in the analysis. The median age was 62 years (IQR 52–71), and 67% were male. Median PFS was 13.24 months (95% CI 7.75–19.12), while median OS was not reached. High SII (≥ 870) was independently associated with shorter PFS in multivariable analysis (OR 5.05; 95% CI 1.14–15.77; p = 0.039). mGPS (1–2) was significantly associated with inferior PFS in Kaplan–Meier analysis (HR 3.43; 95% CI 1.42–8.30; p = 0.006; log-rank p = 0.001), but lost significance in multivariable modeling. Metformin use (OR 0.12; 95% CI 0.02–0.93; p = 0.044), sunitinib therapy (OR 0.07; 95% CI 0.006–0.74; p = 0.027), and favorable/intermediate IMDC risk group (OR 0.17; 95% CI 0.06–0.96; p = 0.047) were independently associated with a lower progression risk. Patients treated with cabozantinib (n = 15) showed a numerically longer median PFS (18.6 months; 95% CI 13.8–23.3) compared with sunitinib (n = 25, 12.2 months; 95% CI 5.5–19.0) and pazopanib (n = 15, 12.1 months; 95% CI 6.7–17.5), although this difference was not statistically significant (log-rank p = 0.152). Conclusion: In this real-world cohort of patients with mccRCC treated with first-line TKI, host-related inflammatory and nutritional status were closely associated with progression-free survival. Additionally, patients classified within the favorable IMDC risk group exhibited a significantly lower risk of progression, highlighting the importance of integrating clinical risk stratification with systemic inflammatory and nutritional markers. Incorporating such easily measurable biomarkers and clinical risk scores into existing prognostic models may enhance individualized risk assessment and therapeutic decision-making. Future prospective, multicenter, randomized controlled, and artificial intelligence–assisted studies are warranted to validate these findings and refine precision oncology approaches in this population.

Long-term oncologic outcomes of metastatic clear-cell renal cell carcinoma after local therapy alone.