Clear cell renal cell carcinoma (ccRCC) is characterized by profound lipid metabolic dysregulation, yet the mechanisms linking peritumoral adipose tissue (PAT)-derived lipid metabolites to tumor aggressiveness remain poorly defined. Here, we identified lysophosphatidylethanolamine 18:1 (LPE18:1), a lipid metabolite enriched in PAT and the arterial blood of ccRCC patients, as a critical driver of tumor growth and lipid deposition. Through multiomics analyses and functional studies, we demonstrated that LPE18:1 upregulates F-actin-capping protein subunit alpha-1 (CAPZA1), which recruits ubiquitin-specific peptidase 48 (USP48) to stabilize the NAD-dependent protein deacetylase sirtuin-6 (SIRT6) by inhibiting its proteasomal degradation. Increased SIRT6 epigenetically promotes acetyl-CoA acetyltransferase 2 (ACAT2) expression, redirecting lipid metabolism toward free cholesterol accumulation-a hallmark of ccRCC aggressiveness. Clinically, CAPZA1 and SIRT6 levels correlate with advanced tumor stage and poor prognosis in ccRCC cohorts. Genetic or pharmacological inhibition of the CAPZA1/SIRT6 axis can reverse LPE18:1-induced lipid deposition and tumor progression in xenograft models. Notably, targeting this axis with the SIRT6 inhibitor OSS-128167 combined with CAPZA1 depletion significantly suppresses ccRCC cell growth. Our study reveals a PAT-derived lipid metabolite-fuelled signaling cascade that reprograms lipid metabolism in ccRCC, identifying CAPZA1/USP48/SIRT6 as actionable therapeutic targets for metabolic malignancies.

Renal cell carcinoma (RCC) is a biologically heterogeneous malignancy accounting for 3% of adult cancers globally. Despite advances in immune checkpoint inhibitors (ICIs) and vascular endothelial growth factor (VEGF)-targeted therapies, durable disease control remains elusive for many patients. Increasing evidence implicates the acidic tumour microenvironment (TME) as a critical mediator of RCC progression, immune evasion, and therapeutic resistance. Solid tumours, including RCC, exhibit reversed pH gradients, characterised by acidic extracellular (pH 6.2–6.9) and alkaline intracellular conditions. This dysregulation arises from enhanced glycolysis, hypoxia-driven lactate accumulation, and the overexpression of pH-regulating enzymes such as carbonic anhydrase (CA9). Acidic TMEs impair cytotoxic T-cell and NK-cell activity, promote tumour-associated macrophage (TAM) polarisation towards an immunosuppressive phenotype, and upregulate alternative immune checkpoints. These mechanisms collectively undermine ICI efficacy and contribute to primary and secondary treatment resistance. Proton-sensing G-protein-coupled receptors (GPCRs), notably GPR65, have emerged as pivotal mediators linking extracellular acidosis to immune dysfunction. Preclinical studies demonstrate that GPR65 antagonists restore anti-tumour immune activity by reversing acidosis-driven immunosuppression and enhancing antigen processing. In RCC models, selective GPR65 inhibitors have shown the ability to reduce immunosuppressive cytokine IL-10 production, induce immunoproteasome activation, and synergise with anti-PD-1 therapy. The first-in-class GPR65 inhibitor, PTT-4256, is now under evaluation in the Phase I/II RAISIC-1 trial (NCT06634849) in solid tumours, including RCC. Targeting acid-sensing pathways represents a novel and promising therapeutic strategy in RCC, aiming to remodel the TME and overcome ICI resistance. Integrating GPR65 inhibition with existing immunotherapies may define the next era of RCC management, warranting continued translational and clinical investigation.

Segmental 3D image-guided robot-assisted partial nephrectomy (3D-IGRAPN) in selected cases of localized renal urothelial carcinoma.

PSMA PET in renal cell carcinoma: an update and future aspects.

Renal cell carcinoma (RCC) during pregnancy is rare and presents a unique clinical dilemma, requiring the simultaneous optimisation of maternal oncological outcomes and fetal safety. Management decisions must balance the urgency of treating a potentially aggressive malignancy against the physiological and obstetric risks of intervention. We present the case of a large, incidentally detected clear cell RCC in a pregnant patient, managed successfully with laparoscopic radical nephrectomy during the second trimester. This case underscores the importance of multidisciplinary collaboration and tailored surgical planning in achieving favourable outcomes for both the mother and fetus.

Antibody-Drug Conjugates in urothelial, prostate, and renal cell cancers: A review of current and emerging therapies.

This study uncovers a direct role for HIF-2 in driving humoral HC of malignancy in ccRCC through transcriptional activation of PTHLH (encoding PTHrP), identifies HC (and PTHrP) as potentially predictive biomarkers of HIF-2 engagement, and sets a foundation for the evaluation of HIF-2 antagonists for HC management in patients.

Reactivity of carbonic anhydrase IX (CA IX) across the spectrum of renal cell carcinomas with sarcomatoid differentiation.

ROCK2 promotes renal cell carcinoma progression by functioning as an RNA-binding protein regulating the PAI-1/NLRP3 axis and senescence escape.

Growth Kinetics of Venous Tumor Thrombus From Renal Cell Carcinoma.

The gold standard treatment for renal cell carcinoma with a tumor thrombus (RCC-TT) is radical nephrectomy with tumor thrombectomy (RN-TT). Operative approaches to this can be done open (ORN-TT), laparoscopic (LRN-TT), or robotic (RRN-TT). The purpose of this study was to compare overall survival (OS), cancer-specific survival (CSS), and metastasis-free survival (MFS) between open, laparoscopic, and robotic approaches to RN-TT using the Intercontinental Collaboration on Renal Cell Carcinoma (ICORCC) database. Patient records were reviewed from the ICORCC database. All patients included in the study underwent RN-TT for RCC-TT from 1999 to present. Tumor thrombus level was graded using the Neves classification system. Statistical analysis was carried out using analysis of variance, chi-squared test, and Kaplan–Meier survival curves with log-rank test to compare outcomes by surgical approach. A total of 392 patients were included. There were 308 ORN-TT, 61 LRN-TT, and 23 RRN-TT cases. On Kaplan–Meier analysis, OS and CSS were not significantly different by approach (p > 0.05). MFS was significantly lower in RRN-TT patients (p = 0.030). Operative time was the longest in ORN-TT, followed by LRN-TT, and RRN-TT the quickest (p = 0.011). Blood transfusion rates were significantly lower in RRN-TT relative to ORN-TT (p < 0.001). Rates of lymph node dissection, soft tissue margin positivity, and cytoreductive surgery were alike (p > 0.05). There is no definitive superiority of one operative approach compared to another. RRN-TT may result in worse MFS for patients, which calls for further investigation, but this is not certain. Ultimately, the risks, benefits, and resources the surgeon has at his/her disposal should all play in the final operative choice of RN-TT for the patient.

Hepatocyte growth factor (HGF) is a multifunctional cytokine that primarily targets epithelial cells. It regulates cell growth, motility, and morphogenesis, promoting tissue regeneration in injured organs. HGF and its receptor (c-Met) play critical roles in regulating numerous biological processes, particularly in kidney diseases. We conducted a literature review to identify the roles of HGF, c-Met, and the HGF/c-Met signaling pathway in kidney diseases, including acute kidney injury (AKI), chronic kidney disease (CKD), the AKI-CKD transition, kidney transplantation, and renal cell carcinoma (RCC). We further explored the regulatory functions of the HGF/c-Met signaling pathway in kidney disease pathology and examined HGF and c-Met as potential therapeutic strategies. We also evaluated the potential of traditional Chinese medicine (TCM) to target the HGF/c-Met pathway in kidney diseases. Our findings may offer new insights for clinical practice and inform future research directions.

Metastatic tumors to the pancreas: An institutional experience.

Structure-activity relationship study of HIF-2α inhibitors with tricyclic scaffold.

Enhancing oral bioavailability of pazopanib via co-amorphous system: Formulation, characterization, pharmacokinetics and toxicity evaluation.

Cabozantinib, a Tyrosine Kinase Inhibitor (TKI), is widely used in Renal Cell Carcinoma (RCC) therapy but often causes serious side effects such as myelosuppression, immunosuppression, and angiopathy. This study aims to identify key protein targets responsible for the therapeutic efficacy and adverse reactions of cabozantinib and to explore structural modifications to reduce toxicity while preserving efficacy. A non-randomized computational approach was employed, screening 400 potential protein targets using SwissTargetPrediction and ChemBL databases. Molecular docking and Structure-Activity Relationship (SAR) analysis were performed to assess interactions between cabozantinib and identified targets, focusing on structural elements contributing to toxicity. Three primary proteins were identified as responsible for the anti-tumor effects of cabozantinib, while three others were linked to its side effects. Docking analysis revealed that the methoxyphenyl group in cabozantinib formed undesirable hydrogen bonds with toxicity-related proteins. Modulating these off-target interactions by minimizing hydrogen bonding in this region could significantly reduce adverse effects. These findings provide structural insights into cabozantinib's dual effects and suggest optimization strategies for TKI design, offering a pathway toward safer and more effective RCC treatments.

Cabozantinib Beyond VEGFR Inhibition: Reprogramming the IO-Refractory Microenvironment in Metastatic RCC

BackgroundUpper tract urothelial carcinoma (UTUC), including renal pelvic urothelial carcinoma and ureter urothelial carcinoma, accounts for 10% of urothelial carcinoma (UC). Poorer outcomes and different genetic characteristics of UTUC were reported compared to urothelial carcinoma of the bladder (UCB), which accounts for most cases of UC. Therefore, there is an urgent need for the development of molecular characterization and precision therapies tailored specifically for UTUC.MethodsTo elucidate the genetic landscape of UTUC, we included 4 UTUC samples in this study and also perform next-generation sequencing (NGS) of whole exome sequencing. After that, long-read sequencing (LRS) was employed to conduct Whole genome sequencing (WGS) analyses on tumor samples obtained from the four UTUC patients, utilizing the Pacific Biosciences (PacBio) REVIO platform.ResultsThe clinical phenotypes of four UTUC patients including tumor stage, location and response to treatment, etc. were collected. NGS of four patients yielded negative results. The WGS mapped the mutation landscape in the tumor tissues of four UTUC patients, and screened the sequencing results according to UTUC and solid tumor related genes. Seven pathogenic or likely pathogenic single nucleotide variant (SNV) were obtained. Among the detected structural variations (SVs), four patients shared multiple segments of SVs with close positions. The 12q24.31-p11.1 inversion was shared by four patients. In the detection of STR and DNA methylation, comparing the results of patients and normal controls, many different fragments were obtained. It shows that LRS has important advantages over NGS for accurate tumor detection and treatment.ConclusionThe analysis revealed multiple genetic variants potentially associated with UTUC carcinogenesis or development, and indicated advantages of TGS over next-generation sequencing (NGS) in cancer genetic variant detection, especially in SV and Short Tandem Repeats (STRs). This study may lay the groundwork for molecular classification and offer valuable insights into the development of precision therapies for UTUC.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12885-025-15254-x.

Local control strategies in pediatric oncology are guided by disease-specific considerations. Effective communication of the goals of surgical procedure and associated intraoperative events plays a crucial role in shaping subsequent treatment decisions. However, accurately and comprehensively documenting these findings remains challenging, with considerable variability across different tumor types. This investigation aims to achieve a consensus on critical intraoperative oncologic observations pertaining to pediatric solid tumors, thereby facilitating the enhancement of surgical reporting and the optimization of subsequent treatment strategies. An expert panel comprising childhood cancer specialists from diverse disciplines and geographical regions participated in a Delphi consensus process. After reviewing relevant literature and engaging in multiple voting rounds, the panel identified essential tumor-specific intraoperative documentation elements. A Delphi panel of 16 experts from diverse geographical locations completed two rounds of voting with a 94% participant retention rate and achieved consensus on 15 key statements. Essential documentation components included completeness of resection, evaluation of locoregional spread, and vascular involvement, with tumor-specific variations. For instance, neuroblastoma required documentation of resection percentage, while sarcoma emphasized biopsy tract resection and plane of resection. Ovarian germ cell tumors necessitated ascitic fluid sampling and contralateral ovary evaluation. Additionally, the presence of tumor thrombus was highlighted as particularly relevant in renal, liver, and adrenocortical carcinomas. Despite recognizing the significance of these findings, the panel noted deficiencies in operative reports, including omissions of documentation of tumor spillage, lymph node sampling, and residual disease, underscoring the need for improved documentation to support multidisciplinary decision-making. This study highlights the critical role of precise intraoperative documentation in guiding multidisciplinary care for pediatric solid tumors. The variability across tumor types underscores the need for tailored documentation guidelines. While a standardized synoptic operative report could improve consistency and communication, a hybrid model combining universal elements with tumor-specific details may offer an effective solution for comprehensive and adaptable reporting.

Long-term Outcomes of Surgical Strategy for Advanced Renal Cell Carcinoma Extending into the Inferior Vena Cava Requiring Intervention by a Vascular Surgeon.