Treatment Of Renal Cell Carcinoma Research Articles

Phospholipase C Beta 2 as a Key Regulator of Tumor Progression and Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Renal Cell Carcinoma

Background: Renal cell carcinoma (RCC) represents the most common form of invasive kidney cancer in adults. Among the components critical to cellular regulation is Phospholipase C Beta 2 (PLCB2), a member of the phospholipase C enzyme family. This enzyme plays a vital role in managing key cellular functions such as growth, differentiation, migration, and survival. Despite its significant importance, the specific expression patterns and molecular mechanisms of PLCB2 in the progression of RCC are not well understood. Methods: This investigation employed a combination of bioinformatics analyses, scRNA-seq, functional assays, transcriptome sequencing, real-time quantitative PCR (RT-PCR), immunofluorescence, rescue experiments, and Western blotting to explore the regulatory function of PLCB2 in driving the epithelial-mesenchymal transition (EMT) in RCC through the PI3K/AKT signaling pathway. Results: PLCB2 expression is significantly elevated in RCC samples, and this increase is inversely correlated with patient prognosis. The knockdown of PLCB2 in RCC cell lines leads to a marked reduction in cell proliferation, invasion, migration, and EMT. Transcriptome sequencing further revealed that PLCB2 is significantly associated with the PI3K/AKT pathway. Notably, the PI3K activator 740Y-P was able to reverse the reductions in migration, invasion, and EMT caused by the PLCB2 knockdown. Conclusions: Our findings underscore the pivotal role of PLCB2 in regulating RCC invasion and metastasis by modulating the EMT via the PI3K/AKT signaling pathway. This highlights PLCB2 not only as a key prognostic biomarker, but also as a promising therapeutic target in the treatment of advanced-stage RCC, offering new avenues for more effective interventions.

Prognostic significance of peripheral blood biomarkers in patients with advanced renal cell carcinoma treated with nivolumab and ipilimumab—a polish multicenter, observational study

Immune checkpoint inhibitors have improved the treatment of metastatic renal cell carcinoma (RCC), with the combination of nivolumab (NIVO) and ipilimumab (IPI) showing promising results. However, not all patients benefit from these therapies, emphasizing the need for reliable, easily assessable biomarkers. This multicenter study involved 116 advanced RCC patients treated with NIVO + IPI across nine oncology centers in Poland. Blood markers such as neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), eosinophils, and monocytes were assessed at baseline, after three months, and before disease progression (PD). The prognostic significance of these parameters was analyzed using linear regression, Kaplan–Meier survival analysis, and Cox regression models. After a median follow-up of 11.8 months, the progression-free survival (PFS) was 12.8 months (95% confidence interval [CI] 5.7–28.1), while the overall survival (OS) was 27.3 months (95% CI 16-not reached). Patients with an NLR increase of ≥ 25% had a PFS of 8.2 (3.1–24.7) months compared to 17.5 (8.6–28.1) months in those with a rise in < 25% (p = 0.015). Similarly, a ≥ 25% increase in PLR was linked to a PFS of 6.8 (2.8–8.3) months compared to 17.4 (8.4–28.1) months (p < 0.001). Multivariate analysis confirmed PLR as an independent predictor of PFS (HR 2.9, 95% CI 1.5–5.6, p = 0.001), while elevated eosinophil levels were associated with a reduced risk of death (HR 0.2, 95% CI 0.04–0.9, p = 0.05). No other analysis was statistically significant. NLR, PLR, and eosinophil levels may serve as valuable biomarkers for predicting treatment response in RCC patients receiving NIVO + IPI.

Avelumab in combination with axitinib and nivolumab in combination with ipilimumab in the first-line treatment of metastatic renal cell carcinoma: a realworld retrospective cohort study

Background: Immunotherapy-based regimens, such as nivolumab plus ipilimumab (Nivo-Ipi) and avelumab plus axitinib (Ave-Axi), are standard first-line treatments for metastatic clear-cell renal cell carcinoma (mRCC) with intermediate or poor IMDC risk. Comparative real-world evidence for these regimens remains limited.Methods: This retrospective cohort study included 102 patients with mRCC treated with Nivo-Ipi (n = 51) or AveAxi (n = 51) from 2018 to 2023. Propensity score matching was used to balance baseline characteristics, including IMDC risk and comorbidities. Primary endpoints were the rate of treatment-related adverse events (TRAEs) and progression-free survival (PFS). Secondary endpoints included objective response rate (ORR) and overall survival (OS).Results: Patient characteristics were balanced across cohorts, with a median age of 63.4 years, 76 % male, and 61 % having chronic cardiovascular diseases. The rate of any grade TRAEs was similar between Nivo-Ipi and Ave-Axi (62.7 % vs. 68.6 %, respectively), as was the rate of grade ≥ 3 TRAEs (11.7 % vs. 17.6 %). Patients treated with Ave-Axi had a significantly extended PFS (15.0 vs 9.7 months; p 0,05). The median OS was not reached.Conclusions: Nivo-Ipi and Ave-Axi are effective and well-tolerated first-line therapies for mRCC in real-world settings. Ave-Axi was associated with a significantly longer PFS and a numerically higher ORR compared to Nivo-Ipi.

Management of renal cell carcinoma with ablation in comparison to nephrectomy: A 5-year analysis of inpatient procedural data to evaluate utilization disparities in the United States.

To perform a nationwide analysis of ablation compared to partial and total nephrectomy for the management of renal cell carcinoma (RCC) to evaluate utilization trends and disparities in the USA. The 2016-2020 National Inpatient Sample was analyzed. Using ICD-10, we identified the diagnosis of RCC then analyzed the utilization trends of ablation and nephrectomies (both partial and complete). To determine if any disparities exist, a multivariate logistic regression was performed to assess the influence of age, sex, race, income, payer, illness severity, geographical location, and hospital factors. From the 183,885 inpatient encounters with RCC, 3045 (1.65%) underwent ablation, 70,080 (38.1%) underwent partial nephrectomy, and 110,760 (60.2%) underwent total nephrectomy. There was no significant difference in the sex between all groups. There was a statistically significant difference in the mean age of those undergoing ablation (67.30, SD=12.05) versus those undergoing partial nephrectomy (59.27, SD=13.26) and total nephrectomy (62.22, SD=14.42) (OR: 1.04, 95%CI: 1.03-1.05, P<0.001). Compared to White patients, Hispanic and African Americans were more likely to undergo ablation versus nephrectomy (OR: 1.52, 95%CI: 1.16-1.98, P=0.002 and OR: 1.65, 95%CI: 1.28-2.13, P<0.001, respectively). Compared to patients on private insurance, those on Medicaid and Medicare were more likely to have ablation than nephrectomy (OR: 1.85, 95%CI: 1.31-2.61, P<0.001, and OR: 1.62, 95%CI: 1.26-2.08, P<0.001, respectively). Furthermore, patients were less likely to undergo ablation than nephrectomies in 2020 compared to 2016 (OR: 0.69, 95%CI: 0.53-0.90, P=0.006). Since 2016, there has been a decreasing trend in the use of ablation for treating RCC in hospitalized patients. Those undergoing ablation tend to be older, African American, Hispanic, and insured by Medicare or Medicaid. Further research is needed to ensure equitable access for optimal treatment of RCC.

A Review of Neoadjuvant Therapy for Localized and Locally Advanced Renal Cell Carcinoma.

The introduction of vascular endothelial growth factor receptor-tyrosine kinases (VEGFR-TKIs) and immune checkpoint inhibitors (IOs) have drastically altered the treatment landscape for kidney cancer, with doublet combination immunotherapy (IO/IO or IO/VEGFR-TKI) now set as the standard front-line treatment for advanced renal cell carcinoma (RCC). However, the roles of VEGFR-TKIs and IOs in the neoadjuvant setting for locoregional/locally advanced RCC remain undefined, where the goals may be primary tumor downsizing/downstaging and potentially eradicating micrometastatic disease. This review will examine VEGFR-TKI monotherapy, IO monotherapy, and VEGFR-TKI/IO combination regimens in a preoperative setting with a focus on the efficacy, toxicity, surgical, and long-term implications.

Efficacy and safety of neoadjuvant therapy with tislelizumab plus axitinib for nonmetastatic renal cell carcinoma with inferior vena cava tumor thrombus: a retrospective study

In renal cell carcinoma (RCC) patients with inferior vena cava (IVC) tumor thrombus, neoadjuvant therapy could alleviate the burden of tumor thrombus, enhance the safety and feasibility of surgical resection, and improve patient prognosis. The combination of tislelizumab and axitinib has demonstrated efficacy in the treatment of advanced RCC. Our study aimed to evaluate the efficacy and safety in the neoadjuvant therapy setting of tislelizumab and axitinib in RCC patients with IVC tumor thrombus. In this retrospective study, seven patients of nonmetastatic RCC with IVC tumor thrombus who received 3 cycles of neoadjuvant therapy with tislelizumab plus axitinib at the First Affiliated Hospital of Xiamen University from May 2020 to December 2023 were included. The main outcomes included objective response rate (ORR), reduction of tumor thrombus size and level, surgical outcomes, and adverse events (AEs). The median age was 66 (range, 50–72) years, and five (71.4%) patients were male. Five (71.4%) patients were diagnosed with clear cell carcinoma, and two (28.6%) patients were papillary type I carcinoma. Four (57.1%) patients had level II tumor thrombus and three (42.9%) patients had level III. The ORR of patients was 57.1%. The mean decrease in thrombus diameter and length was 5.8 (1.8–17.2) mm and 18.5 (4.4–41.5) mm, respectively. All patients showed a decrease in IVC tumor thrombus. The mean time from the end of neoadjuvant therapy to radical nephrectomy and thrombectomy was 31.7(range, 22–45) days. No intraoperative complications or postoperative Clavien-Dindo grade>3 complications occurred. The most common AEs were all grade 1–2, and only one patient had grade 4 hepatic impairment. No AEs delayed the surgery schedule. This study of RCC patients receiving neoadjuvant combination with tislelizumab and axitinib effectively reduced primary tumor and IVC tumor thrombus with the absence of serious AEs, demonstrating a promising neoadjuvant therapy.

Formulation and evaluation of pazopanib-loaded PLGA nanoparticles for enhanced bioavailability and sustained release in cancer chemotherapy

The objective of this study was to develop and characterize a Nano formulation of Pazopanib using poly(DL-lactide-co-glycolide) (PLGA) for improved bioavailability and reduced systemic toxicity. Pazopanib, a tyrosine kinase inhibitor used in the treatment of renal cell carcinoma and soft tissue sarcoma, exhibits limited solubility and bioavailability, restricting its clinical efficacy. We employed an oil-in-water (o/w) emulsion solvent evaporation technique to prepare Pazopanib-loaded PLGA nanoparticles. Various formulations were optimized by adjusting the drug-to-polymer ratio, yielding spherical nanoparticles with an average size of 135 nm and a low polydispersity index, as confirmed by dynamic light scattering and transmission electron microscopy. The nanoparticles demonstrated a high entrapment efficiency of 33.9 ± 2.5% and a zeta potential of -20.12 mV, indicating good colloidal stability. Fourier transform infrared spectroscopy confirmed the compatibility of Pazopanib with PLGA and other excipients. The in vitro drug release studies revealed a sustained release profile over 7 days, contrasting with the rapid release from the free drug solution. These findings suggest that the developed PLGA-based nanoparticulate system could potentially enhance the therapeutic efficacy of Pazopanib by increasing its bioavailability and ensuring controlled release, thus offering a promising approach for cancer chemotherapy.

MTHFD2 Enhances cMYC O-GlcNAcylation to Promote Sunitinib Resistance in Renal Cell Carcinoma.

Sunitinib is a first-line targeted therapy for patients with renal cell carcinoma (RCC), but resistance represents a significant obstacle to the treatment of advanced and metastatic RCC. Metabolic reprogramming is a characteristic of RCC, and changes in metabolic processes might contribute to resistance to sunitinib. Here, we identified MTHFD2, a mitochondrial enzyme involved in one-carbon metabolism, as a critical mediator of sunitinib resistance in RCC. MTHFD2 was elevated in sunitinib resistant RCC cells, and loss of MTHDF2 conferred sensitivity to sunitinib. In patients, MTHFD2 was highly expressed in RCC and was associated with poor outcomes. Mechanistically, MTHFD2 stimulated UDP-GlcNAc biosynthesis and promoted cMYC O-GlcNAcylation by driving the folate cycle. O-GlcNAcylation enhanced cMYC stability and promoted MTHFD2 and CCND1 transcription. Targeting MTHFD2 or cyclin D1 sensitized tumor cells to sunitinib in vitro and in vivo. Consistently, development of a peptide drug capable of efficiently degrading MTHFD2 enabled reversal of sunitinib resistance in RCC. These findings identify a noncanonical metabolic function of MTHFD2 in cell signaling and response to therapy and reveal the interplay between one-carbon metabolism and sunitinib resistance in RCC. Targeting MTHFD2 could be an effective approach to overcome sunitinib resistance.

MULTIDISCIPLINARY APPROACH TO TREATMENT OF PATIENT WITH BIOPROSTHETIC AORTIC VALVE DYSFUNCTION AND RENAL CELL CARCINOMA WITH TUMOR THROMBUS

HighlightsThis review presents a clinical case of a patient with a rare combination of two life-threatening pathologies whose treatment required high-tech surgery. The effectiveness of a multidisciplinary approach to treatment has been demonstrated. AnnotationAortic stenosis (AS) is the most common heart disease in elderly patients requiring treatment. Malignant neoplasms of the kidneys account for about 3% of all cancers in the Russian Federation, and the formation of tumor thrombi in the renal and inferior vena cava occurs in 4–10% of patients with this pathology. Given the prevalence of aortic stenosis and renal cell carcinoma (RCC), the number of patients with a combination of these two conditions keeps increasing and they are recommended to undergo surgical treatment at multidisciplinary clinical centers. Transcatheter aortic valve implantation (TAVI) and radical nephrectomy with intracorporeal thrombectomy using the DaVinci Si robotic surgical system may be a preferred approach for the treatment of critical AS and RCC for this category of patients.At the multidisciplinary clinical center a patient with dysfunctional bioprosthetic aortic valve implanted in 2010 and NYHA class 3 heart failure with history of endovascular treatment of coronary artery disease, peripheral arterial disease and carotid endarterectomy and concomitant renal cell carcinoma with tumor thrombosis of the renal vein received surgical treatment in 2 stages: TAVI – the first stage, and robot-assisted right-sided nephrectomy and thrombectomy from the renal vein – the second stage. The patient was discharged from the Center on the 7th day after TAVI and on the 6th day after surgery for renal cancer. Six months after the procedure, there was a decrease in the functional class of heart failure, satisfactory function of the transcatheter aortic valve bioprosthesis, decrease in the size of the left ventricle, decrease in the brain natriuretic peptide, and the absence of cancer progression.

MiR-507 Acts as a Tumor Suppressor in Renal Cell Carcinoma Cells by Targeting STEAP3.

In recent years, there has been a rise in the incidence of renal cell carcinoma (RCC), with metastatic RCC being a prevalent and significant contributor to mortality. While a regulatory role for microRNAs (miRNAs) in the development and progression of RCC has been recognized, their precise functions, molecular mechanisms, and potential clinical implications remain inadequately elucidated. Hence, this study aimed to explore the role of miR-507 in RCC and identify STEAP3 as a downstream target of miR-507. Bioinformatics analysis was used to analyze the expression of miR-507 and STEAP3 in RCC specimens. CCK-8, Transwell, and flow cytometry assays were used to assess the function of miR-507 in RCC cells. The connection between miR-507 and STEAP3 was confirmed through a luciferase reporter assay. The expression level of STEAP3, p53, and xCT was analyzed by western blotting. Bioinformatics analysis showed that miR-507 was expressed at low levels in RCC tissues and was linked to poor overall survival. STEAP3 was found to be significantly upregulated in RCC. Further, STEAP3 was shown to be targeted by miR-507. High levels of miR-507 reduced the expression of STEAP3, leading to stagnant cell viability, apoptosis, and migrative capacity. Whereas miR-507 knockdown reverted such a tendency. The study also discovered that miR-507 exerted its inhibitory effect through the op53/xCT pathway. Within RCC, miR-507 modulates the expression of SETAP3/p53/xCT axis, exhibiting a tumor suppressive effect. These discoveries offer present prospective biomarkers for both surveillance and treatment of RCC.

Severe genital cutaneous toxicity with sunitib.

Sunitinib is an oral drug approved for the treatment of metastatic renal cell carcinoma. Serious cutaneous adverse reactions to sunitinib are rare, and when they occur, discontinuation of the treatment may be needed. A 70-year-old male patient was diagnosed with stage IV clear cell renal carcinoma and received treatment with sunitinib. After a second cycle with a 25% dose reduction, the patient was admitted with a diagnosis of grade 3 genital erythema. After ruling out other common causes, sunitinib was considered the cause of genital erythema and was stopped. Treatment with corticosteroids, topical applications, and morphine was started, with resolution after 18 days of evolution. There are only a few published reports that describe erythema and scaling of the genital skin. As in those few cases, for our patient, the first clinical signs appeared on day 28 of sunitinib treatment, and the lesions disappeared after 2 weeks without the use of the drug. Erythema and scaling reappeared when the drug was reintroduced, with greater severity than what was described in some of the other cases, which even included cases for which the lesions did not reappear. Rare instances of severe and limiting skin toxicity may necessitate treatment suspension and compromise survival, as observed in our case. It is crucial to recognize these skin toxicities and understand their appropriate management strategies to initiate treatment as early as possible, thereby avoiding hospitalizations and enabling the resumption of sunitinib therapy.

Elucidating the anticancer potential of dendrobine in renal cell carcinoma treatment.

Renal cell carcinoma (RCC) is the predominant form of kidney cancer. Despite the significant improvements in survival rates for advanced RCC patients due to targeted therapy and immunotherapy, challenges such as drug resistance and severe adverse reactions continue to hinder effective management. Therefore, there is an urgent need to identify new therapeutic agents for RCC. Natural products, derived from plants, animals, and microorganisms, are increasingly recognized for their potential in treating complex diseases such as cancer. Dendrobine, a natural product extracted from Dendrobium, holds significant anticancer potential. However, its role in anti-RCC therapy remains poorly understood. This study applied network pharmacology to explore the role of Dendrobine in RCC treatment, identifying STAT3 as a key target. Furthermore, a series of in vitro experiments confirmed that Dendrobine inhibits RCC cell growth. CCK-8 assays demonstrated that Dendrobine inhibits RCC cell viability in a concentration-dependent manner, with an IC50 of 142.5μM for 786-O cells and 146.5μM for A498 cells. Clonogenic formation assays and EdU staining confirmed that Dendrobine suppresses RCC cell proliferation. Wound healing and invasion assays showed that Dendrobine inhibits RCC cell migration and invasion. Hoechst 33342/PI co-staining demonstrated that Dendrobine induces apoptosis in RCC cells. Mechanistically, Western blot analysis revealed that Dendrobine targets the PI3K/Akt signaling pathway by inhibiting the expression of p-PI3K, p-Akt, and p-Erk. Overall, this study seeks to elucidate the underlying pharmacological mechanisms and provide new insights for potential therapeutic strategies in RCC.

Glycine Decarboxylase Regulates Renal Carcinoma Progression via Interferon Stimulated Gene Factor 3-Mediated Pathway.

Renal cell carcinoma (RCC) is considered as a "metabolic disease" due to various perturbations in metabolic pathways that could drive cancer development. Glycine decarboxylase (GLDC) is a mitochondrial enzyme that takes part in the oxidation of glycine to support nucleotide biosynthesis via transfer of one-carbon units. Herein, we aimed to investigate the potential role of GLDC in RCC development. We found that GLDC depletion diminished nucleotide synthesis and promoted reactive oxygen species (ROS) generation to repress RCC progression, which was reversed by repletion of deoxynucleosides. Additionally, in vitro and in vivo studies revealed that GLDC plays an important role in regulation of proliferation and tumor growth via interferon stimulated gene factor 3 (ISGF3)-mediated pathway. Expressions of interferon regulatory factor 9 (IRF9) and signal transducer and activator of transcription 2 (STAT2) were elevated in GLDC knock-downed cells and decreased in GLDC over-expressed cells. Double knock-down of STAT2 and IRF9 in GLDC-deficient cells rescued GLDC depletion-induced decrease in cell proliferation. Furthermore, GLDC depletion increased cisplatin-and doxorubicin-induced DNA damage through ISGF3 pathway, leading to cell cycle dysregulation and increased mitotic catastrophe. These findings reveal that GLDC regulates RCC progression via ISFG3-mediated pathway and offers a promising strategy for RCC treatment.

Effectiveness and Mechanism of Resibufogenin on Human Renal Cancer Cell Caki-1.

In this study, we investigated the effect and mechanism of Resibufogenin on renal cell carcinoma based on network pharmacology, molecular docking, and in vitro experiments. The results showed that there were 35 cross-targets between Resibufogenin and renal cell carcinoma. GO and KEGG pathway analyses indicated that Resibufogenin inhibited renal cancer cells through the vascular smooth muscle contraction signalling pathway and EGFR tyrosine kinase inhibitor resistance signaling pathway, and MAPK1, PRKCB, and Resibufogenin had strong associative activities. After different concentrations of Resibufogenin were applied to human renal cancer cells, it was found that the IC50 value was 408.2 nM, 10 nM resibufogenin could significantly inhibit cell migration (p < 0.0001), the percentage of apoptosis and necrosis increased dose-dependently, and the expression of genes of MAPK1 and PRKCB in the cells was significantly reduced (p < 0.001) in a dose-dependent manner. The above results indicate that Resibufogenin can inhibit human renal cell carcinoma through multi-targets and multi-methods, which provides a theoretical basis for the application of Resibufogenin in the treatment of renal cell carcinoma and the development of novel drugs in the future.

Effectiveness of systemic treatments for advanced non-clear cell renal cell carcinoma: a systematic review and meta-analysis.

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous group of malignancies with substantial differences in morphology, genetic profiles, clinical behavior, and prognosis. Optimal treatment for nccRCC remains unclear, largely extrapolated from evidence available for clear cell renal cell carcinoma (ccRCC). This study aimed to compare the efficacy of current mainstream drug treatments for nccRCC to provide clinical treatment guidance for advanced cases. We systematically searched PubMed, Embase, and Cochrane databases for trials published up to January 2, 2024, including controlled and single-arm trials. Primary outcomes included overall response rate (ORR), disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). We selected six randomized controlled trials (RCTs) comparing mammalian target of rapamycin inhibitors (mTORi) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs). These trials included four first-line and two second-line studies, with a total of 398 advanced nccRCC patients. Pooled results showed that VEGFR-TKIs significantly improved PFS compared to mTORi in first-line treatment (relative risk [RR] = 1.387; 95% confidence interval [CI]: 1.04-1.85; p = 0.026). In a single-arm meta-analysis, we included 22 VEGFR-TKI trials, three mTORi trials, 12 immune checkpoint inhibitor (ICI) therapies, five chemotherapy trials, and 10 combination therapy trials. The pooled ORR ranged from 6% (95% CI: 0-16%) to 36% (95% CI: 27-44%), and the pooled DCR ranged from 54% (95% CI: 50-58%) to 81% (95% CI: 70-91%). Subgroup analysis of ICI showed a higher ORR in the PD-L1 positive group compared to the PD-L1 negative group (RR = 3.044; 95% CI: 1.623-5.709; p = 0.001). This systematic review and meta-analysis demonstrate that VEGFR-TKIs improve PFS in first-line treatment compared to mTORi. The single-arm meta-analysis suggest that combination therapies with different mechanisms result in better ORR and DCR. Furthermore, PD-L1 positive patients showed significantly better therapeutic responses with ICI treatment than PD-L1 negative patients.

Asymmetrically PEGylated and amphipathic heptamethine indocyanine dyes potentiate radiotherapy of renal cell carcinoma via mitochondrial targeting

Enhancing the sensitivity of radiotherapy (RT) towards renal cell carcinoma (RCC) remains a challenge because RCC is a radioresistant tumor. In this work, we design and report asymmetrically Polyethylene Glycol (PEG)ylated and amphipathic heptamethine indocyanine dyes for efficient radiosensitization of RCC treatment. They were synthesized by modifying different lengths of PEG chains as hydrophilic moieties on one N-alkyl chain of a mitochondria-targeting heptamethine indocyanine dye (IR-808), and a radiosensitizer 2-nitroimidazole (NM) as a hydrophobic moiety on another N-alkyl chain. The PEG modification significantly improved water solubility, decreased the intermolecular π–π large aggregates, thereby enhanced renal excretion. The asymmetrical and amphipathic modification enhanced the preferential accumulation in renal tumors through self-assembly into small-size nanoparticles in aqueous environment. Radiosensitization was further improved by preferential accumulation in renal tumor cells and their mitochondria as mitochondria play a crucial role in rapid cancer cell growth, metastasis, and RT resistance. Additionally, the modification also increased the abilities of fluorescence emission and photostability, which is meaningful for imaging-guided precise RCC RT. Therefore, our findings may present a theranostic radiosensitizer for renal tumor-targeted imaging and radiosensitization.Graphical

CDC20-Mediated Selective Autophagy Degradation of PBRM1 Affects Immunotherapy for Renal Cell Carcinoma.

Polybromo 1 (PBRM1) inactivating mutations are associated with clinical benefit from immune checkpoint inhibitor treatments in clear cell renal cell carcinoma (ccRCC). However, whether targeting PBRM1 has the potential to enhance immunotherapy efficacy in patients with wild-type PBRM1 and the upstream pathways that regulate PBRM1 protein stability remain unclear. Here, it is demonstrated that PBRM1 knockdown induced M1 macrophage polarization and infiltration, which enhanced the efficacy of anti-PD-1 immunotherapy in RCC. Meanwhile, CDC20 catalyzes K27 ubiquitination of PBRM1 and promotes its degradation via p62-mediated selective autophagy. A bicyclic peptide (PB1-p62) is designed and constructed to target PBRM1 and p62, thereby promoting the degradation of PBRM1. As a result, the efficacy of anti-PD-1 immunotherapy is enhanced, leading to improved overall survival rates in syngeneic mouse tumor models. Overall, this finding suggest the clinical application of PB1-p62 and provide a novel approach for enhancing the effectiveness of immunotherapy in RCC patients with wild-type PBRM1.

EE262 Cost-Consequence Analysis of Cabozantinib in Combination With Nivolumab in Treatment of First-Line Advanced Renal Cell Carcinoma in Germany: A Payer Perspective

EE262 Cost-Consequence Analysis of Cabozantinib in Combination With Nivolumab in Treatment of First-Line Advanced Renal Cell Carcinoma in Germany: A Payer Perspective

EE644 Budget Impact Analysis of Axitinib (Caxetib®) as Second-Line Therapy for the Treatment of Metastatic Renal Cell Carcinoma in a Cohort in Mexico

EE644 Budget Impact Analysis of Axitinib (Caxetib®) as Second-Line Therapy for the Treatment of Metastatic Renal Cell Carcinoma in a Cohort in Mexico

The Current State of the Diagnoses and Treatments for Clear Cell Renal Cell Carcinoma.

Clear cell renal cell carcinoma is the most common form of kidney cancer, accounting for 75% of malignant kidney tumors, and is generally associated with poor patient outcomes. With risk factors including smoking, obesity, and hypertension, all of which have a high prevalence in the United States and Europe, as well as genetic factors including tuberous sclerosis complex and Von Hippel-Lindau syndrome, there is an increasing need to expand our present understanding. The current clear cell renal cell carcinoma knowledge is outdated, with obsolete diagnostic criteria and moderately invasive surgical treatments still prevailing, partially ascribed to its resistance to chemotherapy and radiation therapy. The standard of treatment relies on surgical intervention, including radical nephrectomy and partial nephrectomy, while more recent treatments target neoplastic growth pathways and immune regulation checkpoints.