RESUMO
This work aimed to fabricate a Cloisite 30B-incorporated carboxymethyl cellulose graft copolymer of acrylic acid and itaconic acid hydrogel (Hyd) via a free radical polymerization method for controlled release of Sunitinib malate anticancer drug. The synthesized samples were characterized by FTIR, XRD, TEM, and SEM-dot mapping analyses. The encapsulation efficiency of Hyd and Hyd/Cloisite 30B (6 wt%) was 81 and 93%, respectively, showing the effectiveness of Cloisite 30B in drug loading. An in vitro drug release study showed that drug release from all samples in a buffer solution with pH 7.4 was higher than in a buffer solution with pH 5.5. During 240 min, the cumulative drug release from Hyd/Cloisite 30B (94.97% at pH 7.4) is lower than Hyd (53.71% at pH 7.4). Also, drug-loaded Hyd/Cloisite 30B (6 wt%) demonstrated better antibacterial activity towards S. Aureus bacteria and E. Coli. High anticancer activity of Hyd/Cloisite 30B against MCF-7 human breast cancer cells was shown by the MTT assay, with a MCF-7 cell viability of 23.82 ± 1.23% after 72-hour incubation. Our results suggest that Hyd/Cloisite 30B could be used as a pH-controlled carrier to deliver anticancer Sunitinib malate.
Assuntos
Carboximetilcelulose Sódica , Portadores de Fármacos , Hidrogéis , Indóis , Nanocompostos , Pirróis , Succinatos , Sunitinibe , Sunitinibe/química , Sunitinibe/farmacologia , Humanos , Concentração de Íons de Hidrogênio , Succinatos/química , Succinatos/farmacologia , Carboximetilcelulose Sódica/química , Hidrogéis/química , Indóis/química , Indóis/farmacologia , Nanocompostos/química , Pirróis/química , Pirróis/farmacologia , Portadores de Fármacos/química , Células MCF-7 , Antineoplásicos/farmacologia , Antineoplásicos/química , Resinas Acrílicas/química , Administração Oral , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Liberação Controlada de Fármacos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
BACKGROUND: Sunitinib, a newly developed multi-targeted tyrosine kinase inhibitor (TKI), has become a common therapeutic option for managing advanced renal cell carcinoma (RCC). Examining the mechanism underlying the interaction between sunitinib and isavuconazole was the aim of this effort. METHODS: The concentrations of sunitinib and its primary metabolite, N-desethyl sunitinib, were analyzed and quantified using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Our study evaluated the potential interaction between isavuconazole and sunitinib using rat liver microsomes (RLM), human liver microsomes (HLM), and in vivo rat models. For the in vivo study, two groups (n = 5) of Sprague-Dawley (SD) rats were randomly allocated to receive sunitinib either with or without co-administration of isavuconazole. Additionally, the effects of isavuconazole on the metabolic stability of sunitinib and N-desethyl sunitinib were studied in RLM in vitro. RESULTS: Our findings demonstrated that in RLM, isavuconazole exhibited a mixed non-competitive and competitive inhibition mechanism, with an IC50 (half maximal inhibitory concentration) value of 1.33 µM. Meanwhile, in HLM, isavuconazole demonstrated a competitive inhibition mechanism, with an IC50 of 5.30 µM. In vivo studies showed that the presence of isavuconazole significantly increased the pharmacokinetic characteristics of sunitinib, with the AUC(0ât), AUC(0â∞), and Tmax rising to approximately 211.38%, 203.92%, and 288.89%, respectively, in contrast to the control group (5 mg/kg sunitinib alone). The pharmacokinetic characteristics of the metabolite N-desethyl sunitinib in the presence of isavuconazole remained largely unchanged compared to the control group. Furthermore, in vitro metabolic stability experiments revealed that isavuconazole inhibited the metabolic processing of both sunitinib and N-desethyl sunitinib. CONCLUSIONS: Isavuconazole had a major impact on sunitinib metabolism, providing fundamental information for the precise therapeutic administration of sunitinib.
Assuntos
Interações Medicamentosas , Indóis , Microssomos Hepáticos , Nitrilas , Piridinas , Pirróis , Sunitinibe , Triazóis , Sunitinibe/farmacologia , Sunitinibe/farmacocinética , Animais , Piridinas/farmacocinética , Piridinas/farmacologia , Ratos , Nitrilas/farmacocinética , Nitrilas/farmacologia , Humanos , Microssomos Hepáticos/metabolismo , Microssomos Hepáticos/efeitos dos fármacos , Pirróis/farmacocinética , Pirróis/farmacologia , Triazóis/farmacocinética , Triazóis/farmacologia , Indóis/farmacocinética , Indóis/farmacologia , Antineoplásicos/farmacocinética , Antineoplásicos/farmacologia , Masculino , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismoRESUMO
The treatment landscape for metastatic renal cell carcinoma (RCC) has advanced significantly with first-line immunotargeted therapy combinations. However, no statistically significant differences were observed in the cohort of patients with favorable risk and some oncologists continue to use sunitinib in these patients. PD-L1 expression has emerged as a negative prognostic factor in RCC, particularly in sunitinib-treated patients, where higher PD-L1 levels are linked to worse outcomes. This article discusses the potential risks associated with the use of sunitinib in PD-L1-positive patients.
Assuntos
Antígeno B7-H1 , Carcinoma de Células Renais , Neoplasias Renais , Sunitinibe , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Sunitinibe/uso terapêutico , Neoplasias Renais/tratamento farmacológico , Antineoplásicos/uso terapêutico , PrognósticoRESUMO
Background: There is interest in using treatment breaks in oncology, to reduce toxicity without compromising efficacy. Trial design: A Phase II/III multicentre, open-label, parallel-group, randomised controlled non-inferiority trial assessing treatment breaks in patients with renal cell carcinoma. Methods: Patients with locally advanced or metastatic renal cell carcinoma, starting tyrosine kinase inhibitor as first-line treatment at United Kingdom National Health Service hospitals. Interventions: At trial entry, patients were randomised (1 : 1) to a drug-free interval strategy or a conventional continuation strategy. After 24 weeks of treatment with sunitinib/pazopanib, drug-free interval strategy patients took up a treatment break until disease progression with additional breaks dependent on disease response and patient choice. Conventional continuation strategy patients continued on treatment. Both trial strategies continued until treatment intolerance, disease progression on treatment, withdrawal or death. Objective: To determine if a drug-free interval strategy is non-inferior to a conventional continuation strategy in terms of the co-primary outcomes of overall survival and quality-adjusted life-years. Co-primary outcomes: For non-inferiority to be concluded, a margin of ≤ 7.5% in overall survival and ≤ 10% in quality-adjusted life-years was required in both intention-to-treat and per-protocol analyses. This equated to the 95% confidence interval of the estimates being above 0.812 and -0.156, respectively. Quality-adjusted life-years were calculated using the utility index of the EuroQol-5 Dimensions questionnaire. Results: Nine hundred and twenty patients were randomised (461 conventional continuation strategy vs. 459 drug-free interval strategy) from 13 January 2012 to 12 September 2017. Trial treatment and follow-up stopped on 31 December 2020. Four hundred and eighty-eight (53.0%) patients [240 (52.1%) vs. 248 (54.0%)] continued on trial post week 24. The median treatment-break length was 87 days. Nine hundred and nineteen patients were included in the intention-to-treat analysis (461 vs. 458) and 871 patients in the per-protocol analysis (453 vs. 418). For overall survival, non-inferiority was concluded in the intention-to-treat analysis but not in the per-protocol analysis [hazard ratio (95% confidence interval) intention to treat 0.97 (0.83 to 1.12); per-protocol 0.94 (0.80 to 1.09) non-inferiority margin: 95% confidence interval ≥ 0.812, intention to treat: 0.83 > 0.812 non-inferior, per-protocol: 0.80 < 0.812 not non-inferior]. Therefore, a drug-free interval strategy was not concluded to be non-inferior to a conventional continuation strategy in terms of overall survival. For quality-adjusted life-years, non-inferiority was concluded in both the intention-to-treat and per-protocol analyses [marginal effect (95% confidence interval) intention to treat -0.05 (-0.15 to 0.05); per-protocol 0.04 (-0.14 to 0.21) non-inferiority margin: 95% confidence interval ≥ -0.156]. Therefore, a drug-free interval strategy was concluded to be non-inferior to a conventional continuation strategy in terms of quality-adjusted life-years. Limitations: The main limitation of the study is the fewer than expected overall survival events, resulting in lower power for the non-inferiority comparison. Future work: Future studies should investigate treatment breaks with more contemporary treatments for renal cell carcinoma. Conclusions: Non-inferiority was shown for the quality-adjusted life-year end point but not for overall survival as pre-defined. Nevertheless, despite not meeting the primary end point of non-inferiority as per protocol, the study suggested that a treatment-break strategy may not meaningfully reduce life expectancy, does not reduce quality of life and has economic benefits. Although the treating clinicians' perspectives were not formally collected, the fact that clinicians recruited a large number of patients over a long period suggests support for the study and provides clear evidence that a treatment-break strategy for patients with renal cell carcinoma receiving tyrosine kinase inhibitor therapy is feasible. Trial registration: This trial is registered as ISRCTN06473203. Funding: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment Programme (NIHR award ref: 09/91/21) and is published in full in Health Technology Assessment; Vol. 28, No. 45. See the NIHR Funding and Awards website for further award information.
Treatment breaks in cancer are of significant interest to patients and health professionals. Renal cell carcinoma is the most common type of kidney cancer. Sunitinib and pazopanib are both targeted treatments. They were commonly used to treat advanced kidney cancer but often cause side effects, sometimes requiring use of a reduced dose or even stopping treatment. The STAR trial was designed to see whether planned treatment breaks made patients with advanced kidney cancer being treated with sunitinib and pazopanib feel better, without substantially affecting how well the treatment worked. After 24 weeks of treatment, patients took sunitinib and pazopanib either as they normally would or in the alternative way with planned treatment breaks. Treating patients in this way was continued until drug-related side effects stopped treatment, patients' disease worsened while taking treatment or the patient died. The trial compared how well the different treatment strategies worked in terms of how long patients lived and their quality of life over that time. This trial is the largest United Kingdom trial in advanced renal cell carcinoma. Patients took part from 60 United Kingdom centres between 2012 and 2017. It was funded by the National Institute for Health and Care Research Health Technology Assessment Programme and run by the Leeds Clinical Trials Research Unit. In total, 920 patients took part. Four hundred and sixty-one patients were allocated to continue treatment and 459 were allocated to start at least one treatment break. Treatment breaks lasted on average 87 days. The length of time patients lived in both arms of the trial appeared similar, but this cannot be concluded due to insufficient information. Being allocated to have treatment breaks rather than continuing treatment did not negatively impact a patient's quality of life. Additionally, allocating patients to have treatment breaks was shown to have significant cost savings compared to just continuing treatment. Importantly planned treatment breaks were shown to be feasible.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Inibidores de Proteínas Quinases , Anos de Vida Ajustados por Qualidade de Vida , Humanos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Carcinoma de Células Renais/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Reino Unido , Suspensão de Tratamento , Sunitinibe/uso terapêutico , Avaliação da Tecnologia Biomédica , Adulto , Antineoplásicos/uso terapêuticoRESUMO
High invasive capacity and acquired tyrosine kinase inhibitors (TKI) resistance of kidney renal clear cell carcinoma (KIRC) cells remain obstacles to prolonging the survival time of patients with advanced KIRC. In the present study, we reported that sine oculis homeobox 1 (SIX1) was upregulated in sunitinib-resistant KIRC cells and metastatic KIRC tissues. Subsequently, we found that SIX1 mediated metastasis and sunitinib resistance via Focal adhesion (FA) signaling, and knockdown of SIX1 enhanced the antitumor efficiency of sunitinib in KIRC. Mechanistically, Integrin subunit beta 1 (ITGB1), an upstream gene of FA signaling, was a direct transcriptional target of SIX1. In addition, we showed that DExH-box helicase 9 (DHX9) was an important mediator for SIX1-induced ITGB1 transcription, and silencing the subunits of SIX1/DHX9 complex significantly reduced transcription of ITGB1. Downregulation of SIX1 attenuated nuclear translocation of DHX9 and abrogated the binding of DHX9 to ITGB1 promoter. Collectively, our results unveiled a new signal axis SIX1/ITGB1/FAK in KIRC and identified a novel therapeutic strategy for metastatic KIRC patients.
Assuntos
Carcinoma de Células Renais , RNA Helicases DEAD-box , Resistencia a Medicamentos Antineoplásicos , Adesões Focais , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio , Integrina beta1 , Neoplasias Renais , Metástase Neoplásica , Transdução de Sinais , Sunitinibe , Humanos , Resistencia a Medicamentos Antineoplásicos/genética , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/metabolismo , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/metabolismo , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Linhagem Celular Tumoral , Integrina beta1/genética , Integrina beta1/metabolismo , Animais , Adesões Focais/genética , Adesões Focais/metabolismo , RNA Helicases DEAD-box/genética , RNA Helicases DEAD-box/metabolismo , Camundongos , Transcrição Gênica , Integrinas/metabolismo , Integrinas/genética , Quinase 1 de Adesão FocalRESUMO
Liver cancers, including hepatocellular carcinoma (HCC), are the sixth most common cancer and the third leading cause of cancer-related death worldwide, representing a global public health problem. This study evaluated nine patients with HCC. Six of the cases involved hepatic explants, and three involved hepatic segmentectomy for tumor resection. Eight out of nine tumors were HCC, with one being a combined hepatocellular-cholangiocarcinoma tumor. Conventional markers of hepatocellular differentiation (Hep Par-1, arginase, pCEA, and glutamine synthetase) were positive in all patients, while markers of hepatic precursor cells (CK19, CK7, EpCAM, and CD56) were negative in most patients, and when positive, they were detected in small, isolated foci. Based on in silico analysis of HCC tumors from The Cancer Genome Atlas database, we found that Hedgehog (HH) pathway components (GLI1, GLI2, GLI3 and GAS1) have high connectivity values (module membership > 0.7) and are strongly correlated with each other and with other genes in biologically relevant modules for HCC. We further validated this finding by analyzing the gene expression of HH components (PTCH1, GLI1, GLI2 and GLI3) in our samples through qPCR, as well as by immunohistochemical analysis. Additionally, we conducted a chemosensitivity analysis using primary HCC cultures treated with a panel of 18 drugs that affect the HH pathway and/or HCC. Most HCC samples were sensitive to sunitinib. Our results offer a comprehensive view of the molecular landscape of HCC, highlighting the significance of the HH pathway and providing insight into focused treatments for HCC.
Assuntos
Carcinoma Hepatocelular , Proteínas Hedgehog , Neoplasias Hepáticas , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Regulação Neoplásica da Expressão Gênica , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Proteína GLI1 em Dedos de Zinco/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Transdução de Sinais , Sunitinibe/farmacologia , Sunitinibe/uso terapêutico , Adulto , Proteína Gli2 com Dedos de Zinco/metabolismo , Proteína Gli2 com Dedos de Zinco/genéticaRESUMO
BACKGROUND: Sunitinib, a multi-targeted tyrosine kinase inhibitor, is used as a second-line therapy for gastrointestinal stromal tumors (GIST) resistant to imatinib. However, its impact on the vascular endothelial growth factor (VEGF) pathway can lead to significant toxicities, including hypertension and thrombotic microangiopathy (TMA). CASE PRESENTATION: This case report describes a unique instance of a patient with metastatic GIST who developed endocapillary proliferative glomerulonephritis (EPGN) with IgA2 deposits and TMA following sunitinib treatment. The patient presented with severe hypertension, nephrotic syndrome, and acute kidney injury. Renal biopsy confirmed the diagnosis, revealing IgA2 deposits, which are not commonly associated with TMA. Discontinuation of sunitinib led to a rapid improvement in renal function and proteinuria. The potential mechanisms underlying sunitinib-induced glomerular injury may involve the blockade of VEGFR-1, affecting immune cell recruitment and function, and the disruption of the nitric oxide and endothelin systems, leading to endothelial damage and immune dysregulation. Management of these toxicities requires a personalized approach, with options ranging from symptomatic relief to drug discontinuation. The use of endothelin receptor antagonists and other therapeutic alternatives for GIST management is discussed. CONCLUSIONS: This case highlights the complex interplay between the therapeutic effects of sunitinib and its potential renal and cardiovascular toxicities, emphasizing the need for close monitoring and effective management strategies to optimize patient outcomes.
Assuntos
Antineoplásicos , Tumores do Estroma Gastrointestinal , Sunitinibe , Microangiopatias Trombóticas , Humanos , Sunitinibe/uso terapêutico , Sunitinibe/efeitos adversos , Microangiopatias Trombóticas/induzido quimicamente , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Masculino , Imunoglobulina A/metabolismo , Glomerulonefrite por IGA/patologia , Glomerulonefrite Membranoproliferativa/induzido quimicamente , Glomerulonefrite Membranoproliferativa/patologia , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Pessoa de Meia-Idade , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/patologiaRESUMO
BACKGROUND: Metastatic Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors characterized by high morbidity and limited systemic treatment options, mainly based on radiometabolic treatments or chemotherapy. Based on the preclinical rationale that PGGLs carcinogenesis relies on angiogenesis, treatment with tyrosine kinase inhibitors (TKI) may represent another viable therapeutic option. METHODS: We conducted a prospective phase II study in patients with metastatic or unresectable PGGLs. Patients received sunitinib (50 mg daily for 4 weeks, followed by a 2-week rest period) until progressive disease (PD), unacceptable toxicity or consent withdrawal. The primary endpoint was 12-month progression-free survival (PFS) rate; secondary endpoints were safety overall response rate (ORR) according to RECIST 1.1 criteria and overall survival (OS). EudraCT Number: 2011-002632-99. RESULTS: Fifty patients were included. At a median follow-up of 71.7 months (IQR 35.4-100.1), the 1 year-PFS rate was 53.4 % (95 %CI 41.1-69.3) and median PFS was 14.1 months (95 % CI 8.9-25.7). ORR was 15.6 %, the median OS was 49.4 months (95 %CI 21.2-NA), and grade 3 or higher treatment-related adverse events were reported in 34 % patients. No significant correlation was found between specific genetic alterations or genomic clusters and sunitinib efficacy. CONCLUSION: Sunitinib is an active drug in patients with advanced PGGLs, capable of inducing prolonged disease control with a manageable toxicity profile.
Assuntos
Neoplasias das Glândulas Suprarrenais , Paraganglioma , Feocromocitoma , Sunitinibe , Humanos , Sunitinibe/uso terapêutico , Sunitinibe/efeitos adversos , Feminino , Masculino , Pessoa de Meia-Idade , Feocromocitoma/tratamento farmacológico , Feocromocitoma/patologia , Paraganglioma/tratamento farmacológico , Paraganglioma/patologia , Neoplasias das Glândulas Suprarrenais/tratamento farmacológico , Idoso , Adulto , Estudos Prospectivos , Antineoplásicos/uso terapêutico , Antineoplásicos/efeitos adversos , Intervalo Livre de ProgressãoRESUMO
BACKGROUND: Hepatic ischemia reperfusion injury (IRI) is a common liver surgery complication. This study aims to explore the effect and potential mechanism of Sunitinib - a multi-target tyrosine kinase inhibitor - on hepatic IRI. METHODS: We established a hepatic IRI model using C57BL/6 mice, and integrated 40 mg/kg of Sunitinib, solely or combined with 100 µg/kg of coumermycin A1 (C-A1), in the treatment strategy. H&E staining, TUNEL assay, and detection of serum ALT and AST activities were used to assess liver damage. Further, ELISA kits and Western Blots were utilized to determine IL-1ß, TNF-α, IL-6, CXCL10, and CXCL2 levels. Primary macrophages, once isolated, were cultured in vitro with either 2 nM of Sunitinib, or Sunitinib in conjunction with 1 µM of C-A1, to gauge their influence on macrophage polarization. qPCR and Western blot were conducted to examine the level of p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2, and M1/M2 polarization markers. To quantify immune cell infiltration, we applied Immunofluorescence. RESULTS: Sunitinib pretreatment significantly alleviated liver injury and reduced p-STAT1/STAT1, p-STAT3/STAT3, p-JAK2/JAK2 levels. In vitro, Sunitinib treatment curbed M1 polarization induced by LPS + IFN-γ and bolstered M2 polarization triggered by IL-4. C-A1 application upregulated JAK2/STAT pathway phosphorylation and promoted LPS + IFN-γ-induced M1 polarization, which was reversed by Sunitinib treatment. In IL-4-stimulated macrophages, application of C-A1 activated the JAK2/STAT pathway and decreased M2-type macrophages, which was reversed by Sunitinib treatment either. CONCLUSION: Sunitinib is capable of guiding the polarization of macrophages toward an M2-type phenotype via the inhibition of the JAK2/STAT pathway, thereby exerting a protective effect on hepatic IRI.
Assuntos
Janus Quinase 2 , Macrófagos , Camundongos Endogâmicos C57BL , Traumatismo por Reperfusão , Transdução de Sinais , Sunitinibe , Animais , Janus Quinase 2/metabolismo , Janus Quinase 2/antagonistas & inibidores , Sunitinibe/farmacologia , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/imunologia , Masculino , Transdução de Sinais/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Fatores de Transcrição STAT/metabolismoRESUMO
A sophisticated electrochemical sensor is presented employing a glassy carbon electrode (GCE) modified with a novel composite of synthesized graphitic carbon nitride (g-C3N4) and CoNiO2 bimetallic oxide nanoparticles (g-C3N4/CoNiO2). The sensor's electrocatalytic capabilities for Sunitinib (SUNI) oxidation were demonstrated exceptional performance with a calculated detection limit (LOD) of 52.0 nM. The successful synthesis and integrity of the composite were confirmed through meticulous characterization using various techniques. FT-IR analysis affirmed the successful synthesis of g-C3N4/CoNiO2 by providing insights into its molecular structure. XRD, FE-SEM, SEM-EDX, and BET analyses collectively validated the material's structural integrity, surface morphology, and electrocatalytic performance. Optimization of key analytical parameters, such as loading volume, concentration, electrolyte solution type, and pH, enhanced the electrocatalytic sensing capabilities of g-C3N4/CoNiO2. The synergistic interaction between g-C3N4 and CoNiO2 bimetallic oxide nanoparticles executed the sensor highly effective in the electrical oxidation of SUNI. Across a concentration range of 0.1-83.8 µM SUNI, the anodic peak current exhibited a linear increase with good precision. Application of the newly developed g-C3N4/CoNiO2 system to detect SUNI in a variety of samples, including urine, human serum, and capsule dosage forms, obtained satisfactory recoveries ranging from 97.1 to 103.0%. This methodology offers a novel approach to underscore the potential of the developed sensor for applications in biological and pharmaceutical monitoring.
Assuntos
Técnicas Eletroquímicas , Eletrodos , Grafite , Limite de Detecção , Compostos de Nitrogênio , Sunitinibe , Grafite/química , Humanos , Sunitinibe/química , Sunitinibe/análise , Sunitinibe/sangue , Sunitinibe/urina , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Compostos de Nitrogênio/química , Nanopartículas Metálicas/química , Carbono/química , Óxidos/química , Oxirredução , Nitrilas/químicaRESUMO
INTRODUCTION: Introduction: Renal cell carcinoma (RCC) is a very rare pediatric renal tumor. Robust evidence to guide treatment is lacking and knowledge on targeted therapies and immunotherapy is mainly based on adult studies. Currently, the International Society of Pediatric Oncology-Renal Tumor Study Group (SIOP-RTSG) 2016 UMBRELLA protocol recommends sunitinib for metastatic or unresectable RCC. METHODS: This retrospective study describes the effects of tyrosine kinase inhibitors (TKI), anti-programmed cell death 1 (PD-(L)1) monoclonal antibodies, and immunotherapeutic regimens in advanced-stage and relapsed pediatric RCC. RESULTS: Of the 31 identified patients (0-18 years) with histologically proven RCC, 3/31 presented with TNM stage I/II, 8/31 with TNM stage III, and 20/31 with TNM stage IV at diagnosis. The majority were diagnosed with translocation type RCC (MiT-RCC) (21/31) and the remaining patients mainly presented with papillary or clear-cell RCC. Treatment in a neoadjuvant or adjuvant setting, or upon relapse or progression, included mono- or combination therapy with a large variety of drugs, illustrating center specific choices in most patients. Sunitinib was often administered as first choice and predominantly resulted in stable disease (53%). Other frequently used drugs included axitinib, cabozantinib, sorafenib, and nivolumab; however, no treatment seemed more promising than sunitinib. Overall, 15/31 patients died of disease, 12/31 are alive with active disease, and only four patients had a complete response. The sample size and heterogeneity of this cohort only allowed descriptive statistical analysis. CONCLUSION: This study provides an overview of a unique series of clinical and treatment characteristics of pediatric patients with RCC treated with targeted therapies.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Criança , Estudos Retrospectivos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Masculino , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Feminino , Adolescente , Pré-Escolar , Lactente , Terapia de Alvo Molecular , Sunitinibe/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Recém-Nascido , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores de Checkpoint Imunológico/uso terapêutico , Estadiamento de NeoplasiasRESUMO
OBJECTIVE: To evaluate the clinical significance of subtyping (type 1 vs 2) of papillary renal cell carcinoma (PRCC) in patients treated with targeted therapy, as well as the concordance, sensitivity and positive predictive value (PPV) of local review pathology review. METHODS: Patients with advanced refractory PRCC were randomised to receive sunitinib or cabozantinib, crizotinib or savolitinib, stratified by PRCC subtype (type 1, type 2, or not otherwise specified [NOS]/mixed) by local review. Central review was retrospectively conducted by three expert genitourinary pathologists who independently reviewed cases. The sensitivity and PPV of local review were estimated and outcomes [objective response rate (ORR), progression-free survival (PFS)] were summarised for treatment groups stratified by subtypes by central review. RESULTS: Amongst the 147 patients reviewed, the prevalence of individual subtypes varied by local or central review (type 1: 17.7% vs 29.3%; type 2: 53.1% vs 45.6%; NOS/mixed: 29.3% vs 25.2%), respectively. Individual cases were frequently reclassified and local pathology review demonstrated low sensitivity (type 1: 48%, 95% confidence interval [CI] 33, 65; type 2: 67%, 95% CI 55, 78; NOS/mixed: 43%, 95% CI 27, 61). The PPVs of local review were 80%, 57.7% and 37% for type 1, 2 and NOS/mixed, respectively. Compared to sunitinib, cabozantinib demonstrated improved PFS for both type 1 and type 2 PRCC subgroups (7.4 vs 9.0 and 2.9 vs 5.6 months, respectfully) as well as higher ORR. CONCLUSIONS: The PRCC subtype assignment did not identify a subset of patients with greater clinical benefit from cabozantinib, with significant discordance between local and central review. Our findings confirm the limited clinical value of pathological subtyping of metastatic PRCC, in line with the recent World Health Organisation 2022 guidelines. PATIENT SUMMARY: In this study, categorising papillary renal cell carcinoma into type 1 or 2 subtypes showed limited concordance between central and local pathological review and did not enrich for patients more likely to benefit from cabozantinib in the S1500 PAPMET trial.
Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/classificação , Neoplasias Renais/patologia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/classificação , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Adulto , Sunitinibe/uso terapêutico , Anilidas/uso terapêutico , Antineoplásicos/uso terapêutico , Piridinas/uso terapêuticoRESUMO
This article reports a spectrofluorometric method for the determination of sunitinib (STB) drug based on molecularly imprinted nanofibers fabricated by the electrospinning method and modified by magnetic nanoparticles as sorbent. The characterization of magnetic molecularly imprinted nanofibers (MMINs) was carried out using X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscopy (TEM), which confirmed the successful synthesis of MMINs with well-distributed magnetite nanoparticles. Drug adsorption and desorption were optimized and important parameters such as sample pH, nanofiber mass, adsorption and desorption time, eluent solvent and sample volume were analyzed. The results demonstrated that the MMINs act as a selective sorbent for STB and can be readily collected through an external magnetic field. Methanol was used as the best eluent solvent for STB desorption from MNIN. A linear correlation was observed between the STB concentrations and fluorescence intensities in the range of 0.01-15.0 mg L-1. The detection limit for this method was 0.002 mg L-1. The relative standard deviation (RSD) of 2.6 % for 1.0 mg L-1 and 1.1 % for 10 mg L-1 of STB (n = 3) were obtained, which indicates that the developed method is precise in determining STB. Human serum and capsule analysis show the applicability of the proposed sensor for real samples.
Assuntos
Impressão Molecular , Nanofibras , Sunitinibe , Humanos , Sunitinibe/sangue , Sunitinibe/química , Sunitinibe/análise , Nanofibras/química , Cápsulas , Indóis/química , Indóis/sangue , Limite de Detecção , Nanopartículas de Magnetita/química , Pirróis/química , Adsorção , Espectrometria de Fluorescência/métodosRESUMO
BACKGROUND: Immunotherapy-based combinations have emerged as standard therapies for patients with metastatic renal cell carcinoma (mRCC). Pembrolizumab, a PD-1 inhibitor, combined with epacadostat, an indoleamine 2,3-deoxygenase 1 selective inhibitor, demonstrated promising antitumor activity in a phase 1 study in advanced solid tumors, including mRCC. METHODS: KEYNOTE-679/ECHO-302 was a randomized, open-label, parallel-group, multicenter, phase 3 study (NCT03260894) that compared pembrolizumab plus epacadostat with sunitinib or pazopanib as first-line treatment for mRCC. Eligible patients had histologically confirmed locally advanced or metastatic clear cell RCC and had not received systemic therapy. Patients were randomly assigned 1:1 to pembrolizumab 200 mg IV every 3 weeks plus epacadostat 100 mg orally twice daily versus sunitinib 50 mg orally once daily (4 weeks on treatment followed by 2 weeks off treatment) or pazopanib 800 mg orally once daily. Original dual primary end points were progression-free survival and overall survival. Enrollment was stopped when a phase 3 study in melanoma of pembrolizumab plus epacadostat compared with pembrolizumab monotherapy did not meet its primary end point. This protocol was amended, and primary end point was changed to investigator-assessed objective response rate (ORR) per RECIST 1.1. RESULTS: One-hundred-twenty-nine patients were randomly assigned to receive pembrolizumab plus epacadostat (n = 64) or sunitinib/pazopanib (n = 65). Median (range) follow-up, defined as time from randomization to data cutoff, was 10.3 months (2.2-14.3) and 10.3 months (2.7-13.8) in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. ORRs were similar between pembrolizumab plus epacadostat (31.3% [95% CI 20.2-44.1] and sunitinib/pazopanib (29.2% [18.6-41.8]). Grade 3-5 treatment-related adverse events occurred in 34.4% and 42.9% of patients in the pembrolizumab plus epacadostat and sunitinib/pazopanib arms, respectively. One patient in the sunitinib/pazopanib arm died of septic shock (not treatment-related). Circulating kynurenine levels decreased in the pembrolizumab plus epacadostat arm, but not to levels observed in healthy subjects. CONCLUSIONS: ORRs were similar between pembrolizumab plus epacadostat and sunitinib/pazopanib as first-line treatment in patients with mRCC. Safety and tolerability appeared similar between treatment arms; no new safety concerns were identified. Antitumor responses observed in patients with RCC receiving pembrolizumab plus epacadostat may be driven primarily by pembrolizumab. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; NCT03260894 .
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renais , Indazóis , Neoplasias Renais , Pirimidinas , Sulfonamidas , Sunitinibe , Humanos , Carcinoma de Células Renais/tratamento farmacológico , Sunitinibe/uso terapêutico , Sunitinibe/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/uso terapêutico , Sulfonamidas/efeitos adversos , Masculino , Feminino , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Pessoa de Meia-Idade , Pirimidinas/uso terapêutico , Pirimidinas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Idoso , Indazóis/administração & dosagem , Indazóis/uso terapêutico , Adulto , Idoso de 80 Anos ou mais , OximasRESUMO
INTRODUCTION: The administration of proton pump inhibitors (PPIs) is a common practice to reduce gastro-esophageal adverse events associated with drug treatments but may impair absorption and exposure to oncology drugs. This study investigated the effect of concomitant administration of PPIs and pazopanib, sunitinib and cabozantinib on survival of patients with metastatic clear cell renal carcinoma (mRCC). PATIENTS AND METHODS: Total 451 patients receiving pazopanib, sunitinib and cabozantinib as first line treatment were enrolled in this retrospective study. Patients were defined as "no concomitant PPIs (PPI-)" if no PPIs were administered during TKIs, and as "concomitant PPIs (PPI+)" if the administration of PPIs was at least 75% of the time during which TKIs were given. RESULTS: Eighty patients administered pazopanib were PPI- and 86 PPI+; no difference in PFS was observed (10.7 vs. 11.9 months, P = .79). If patients were stratified as short (n = 89) and long (n = 77) responders, there was a significant difference in terms of PFS in PPI+ (n = 47) versus PPI- (n = 30) in long responders, being 24.7 versus 38 months (P = .04), respectively. In the sunitinib cohort, no significant difference of PFS in PPI+ (n = 102) versus PPI- (n = 131) was found, being 11.3 versus 18.1 months, respectively (P=0.15). In the cabozantinib cohort, there was a statistically significant difference in PFS of PPI+ versus PPI- (6 months vs. not reached, P = .04). No correlation with adverse events was found. CONCLUSIONS: This study demonstrates an association between PPIs and impaired PFS in mRCC patients given pazopanib and cabozantinib and recommends caution on their concomitant use.
Assuntos
Anilidas , Carcinoma de Células Renais , Indazóis , Neoplasias Renais , Inibidores de Proteínas Quinases , Inibidores da Bomba de Prótons , Piridinas , Pirimidinas , Sulfonamidas , Sunitinibe , Humanos , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/efeitos adversos , Inibidores da Bomba de Prótons/uso terapêutico , Masculino , Feminino , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Indazóis/administração & dosagem , Indazóis/efeitos adversos , Estudos Retrospectivos , Pessoa de Meia-Idade , Carcinoma de Células Renais/tratamento farmacológico , Sunitinibe/administração & dosagem , Sunitinibe/efeitos adversos , Sunitinibe/uso terapêutico , Idoso , Pirimidinas/efeitos adversos , Pirimidinas/administração & dosagem , Sulfonamidas/administração & dosagem , Sulfonamidas/efeitos adversos , Sulfonamidas/uso terapêutico , Piridinas/efeitos adversos , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Anilidas/efeitos adversos , Anilidas/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/uso terapêutico , Resultado do Tratamento , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso de 80 Anos ou mais , Interações MedicamentosasRESUMO
BACKGROUND: Most gastrointestinal stromal tumors (GISTs) harbor c-KIT or PDGFRA mutations. Administration of tyrosine kinase inhibitors (TKIs) has significantly improved the survival of patients with GISTs. We aimed to evaluate the clinical outcome of advanced or recurrent GIST patients in Taiwan. METHODS: Patients diagnosed between 2010 and 2020 were enrolled. The collected data included baseline characteristics, treatment pattern, treatment outcome, genetic aberrations and survival status. Progression-free survival (PFS) and overall survival (OS) were analyzed and plotted with the Kaplan-Meier method. Cox regression analysis was used to analyze the prognostic factors of survival. RESULTS: A total of 224 patients with advanced or recurrent GISTs treated with TKIs were enrolled. All patients received imatinib treatment. Ninety-three and 42 patients received sunitinib and regorafenib treatment, respectively. The 48-month PFS and OS rates for patients treated with imatinib were 50.5% and 79.5%, respectively. c-KIT exon 9 and PDGFRA mutations were prognostic factors for a poor PFS and PDGFRA mutation was a prognostic factor for a poor OS in patients treated with imatinib in multivariate Cox regression analysis. The median PFS of patients who received sunitinib treatment was 12.76 months (95% confidence interval (CI), 11.01-14.52). Patients with c-KIT exon 9 mutations had a longer PFS than those with other genetic aberrations. The median PFS of patients treated with regorafenib was 7.14 months (95% CI, 3.39-10.89). CONCLUSIONS: We present real-world clinical outcomes for advanced GIST patients treated with TKIs and identify mutational status as an independent prognostic factor for patient survival.
Assuntos
Tumores do Estroma Gastrointestinal , Mutação , Recidiva Local de Neoplasia , Inibidores de Proteínas Quinases , Proteínas Proto-Oncogênicas c-kit , Receptor alfa de Fator de Crescimento Derivado de Plaquetas , Sistema de Registros , Humanos , Tumores do Estroma Gastrointestinal/tratamento farmacológico , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/patologia , Feminino , Masculino , Taiwan/epidemiologia , Pessoa de Meia-Idade , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Proteínas Proto-Oncogênicas c-kit/genética , Adulto , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/genética , Sunitinibe/uso terapêutico , Mesilato de Imatinib/uso terapêutico , Prognóstico , Idoso de 80 Anos ou mais , Neoplasias Gastrointestinais/tratamento farmacológico , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Taxa de Sobrevida , Intervalo Livre de Progressão , Estimativa de Kaplan-MeierRESUMO
Sunitinib has greatly improved the survival of clear cell renal cell carcinoma (ccRCC) patients in recent years. However, 20-30% of treated patients do not respond. To identify miRNAs and genes associated with a response, comparisons were made between biopsies from responder and non-responder ccRCC patients. Using integrated transcriptomic analyses, we identified 37 miRNAs and 60 respective target genes, which were significantly associated with the NF-kappa B, PI3K-Akt and MAPK pathways. We validated expression of the miRNAs (miR-223, miR-155, miR-200b, miR-130b) and target genes (FLT1, PRDM1 and SAV1) in 35 ccRCC patients. High levels of miR-223 and low levels of FLT1, SAV1 and PRDM1 were associated with worse overall survival (OS), and combined miR-223 + SAV1 levels distinguished responders from non-responders (AUC = 0.92). Using immunohistochemical staining of 170 ccRCC patients, VEGFR1 (FLT1) expression was associated with treatment response, histological grade and RECIST (Response Evaluation Criteria in Solid Tumors) score, whereas SAV1 and BLIMP1 (PRDM1) were associated with metachronous metastatic disease. Using in situ hybridisation (ISH) to detect miR-155 we observed higher tumoural cell expression in non-responders, and non-tumoural cell expression with increased histological grade. In summary, our preliminary analysis using integrated miRNA-target gene analyses identified several novel biomarkers in ccRCC patients that surely warrant further investigation.
Assuntos
Carcinoma de Células Renais , Resistencia a Medicamentos Antineoplásicos , Regulação Neoplásica da Expressão Gênica , Neoplasias Renais , MicroRNAs , Sunitinibe , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/patologia , MicroRNAs/genética , Sunitinibe/uso terapêutico , Sunitinibe/farmacologia , Neoplasias Renais/genética , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Antineoplásicos/uso terapêutico , Antineoplásicos/farmacologia , Perfilação da Expressão Gênica/métodos , Biomarcadores Tumorais/genética , Adulto , Indóis/uso terapêutico , Indóis/farmacologiaRESUMO
A 62-year-old male presenting with gross hematuria and right renal mass was referred to our Urology Department. Computed tomography revealed a right renal mass, with multiple pulmonary lesions. He underwent right nephrectomy for highly suspected renal cell carcinoma with pulmonary metastases (cT3aN0M1). The pathological diagnosis was clear cell renal cell carcinoma, pT1b. Following surgery, he was treated with multiple regimens of chemotherapy, ranging from interferon alpha, multiple tyrosine kinase inhibitors such as sorafenib, axitinib, pazopanib and cabozantinib, everolimus, and nivolumab, all of which were discontinued after its induction, either due to adverse events or progressive disease. He was finally administered Sunitinib as the 8th line "last-ditch" treatment, which resulted in significant tumor shrinkage. No disease progression has been observed 25 months after initiating sunitinib administration.
Assuntos
Antineoplásicos , Carcinoma de Células Renais , Indóis , Neoplasias Renais , Pirróis , Sunitinibe , Humanos , Sunitinibe/uso terapêutico , Masculino , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Pessoa de Meia-Idade , Indóis/uso terapêutico , Pirróis/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/diagnóstico por imagem , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/patologia , Nefrectomia , Tomografia Computadorizada por Raios XRESUMO
INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a rare condition characterized by multiple gas-filled cysts in the gastrointestinal tract and is associated with numerous conditions. Benign PCI can occur secondary to certain medications, such as anticancer-targeted therapies. Here, we report a rare case of PCI that developed following sunitinib therapy for metastatic RCC and was successfully managed with conservative treatment without surgery. PATIENT CONCERNS: A 57-year-old woman with a medical history of metastatic renal cell carcinoma (RCC) referred to the Department of General Surgery after completion of the 16th cycle of sunitinib because of abnormal findings on abdominopelvic computed tomography (CT), suggesting necrotizing enteritis with pneumoperitoneum involving the ileum. At the time of presentation to the Department of General Surgery, she was asymptomatic and had no abnormal findings on examination other than the imaging findings. DIAGNOSIS: Sunitinib-induced PCI, metastatic RCC, liver cirrhosis, and diabetes mellitus. INTERVENTIONS: She was admitted to the general ward for conservative treatment, and sunitinib was discontinued. Conservative treatments included nil per os, total parenteral nutrition, antibiotics, H2-blockers, and oxygen therapy. OUTCOMES: On the fifth day of hospitalization, the PCI showed moderate resolution on plain radiography, and she was discharged on the seventh day. Follow-up CT imaging 3 months later demonstrated complete resolution of PCI. CONCLUSION: This case emphasizes that the decision between conservative versus surgical treatment for PCI should be based not solely on radiological findings but rather on a comprehensive assessment, including the underlying condition, vital signs, physical examinations, and blood tests.
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Antineoplásicos , Carcinoma de Células Renais , Neoplasias Renais , Pneumatose Cistoide Intestinal , Sunitinibe , Humanos , Sunitinibe/efeitos adversos , Feminino , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/secundário , Pneumatose Cistoide Intestinal/induzido quimicamente , Pessoa de Meia-Idade , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/patologia , Antineoplásicos/efeitos adversos , Indóis/efeitos adversos , Indóis/uso terapêutico , Tomografia Computadorizada por Raios X , Pirróis/efeitos adversosRESUMO
BACKGROUND: Sunitinib is a multikinase inhibitor used to treat patients with advanced renal cell carcinoma (RCC). However, sunitinib toxicity makes it a double-edged sword. Potent immune modulation by sunitinib extends to nuclear interactions. To address these issues, there is an urgent need for delivery vectors suitable for sunitinib treatment. METHODS: We developed PEGylated liposomes as delivery vectors to precisely target sunitinib (lipo-sunitinib) to RCC tumors. Further investigations, including RNA sequencing (RNA-seq), were performed to evaluate transcriptomic changes in these pathways. DiI/DiR-labeled lipo-sunitinib was used for the biodistribution analysis. Flow cytometry and immunofluorescence (IF) were used to examine immune modulation in orthotopic RCC models. RESULTS: The evaluation of results indicated that lipo-sunitinib precisely targeted the tumor site to induce autophagy and was readily taken up by RCC tumor cells. In addition, transcriptomic assays revealed that following lipo-sunitinib treatment, autophagy, antigen presentation, cytokine, and chemokine production pathways were upregulated, whereas the epithelial-mesenchymal transition (EMT) pathway was downregulated. In vivo data provided evidence supporting the inhibitory effect of lipo-sunitinib on RCC tumor progression and metastasis. Flow cytometry further demonstrated that liposunitinib increased the infiltration of effector T cells (Teffs) and conventional type 1 dendritic cells (cDC1s) into the tumor. Furthermore, systemic immune organs such as the tumor-draining lymph nodes, spleen, and bone marrow exhibited upregulated anticancer immunity following lipo-sunitinib treatment. CONCLUSION: Our findings demonstrated that lipo-sunitinib is distributed at the RCC tumor site, concurrently inducing potent autophagy, elevating antigen presentation, activating cytokine and chemokine production pathways, and downregulating EMT in RCC cells. This comprehensive approach significantly enhanced tumor inhibition and promoted anticancer immune modulation.