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Comparative safety of tyrosine kinase inhibitors in the treatment of metastatic renal cell carcinoma: a systematic review and network meta-analysis.

Objective: This study aimed to compare the safety profile of tyrosine kinase inhibitors (TKIs) approved for use as monotherapy or combination therapy for the first-line treatment of adult patients with metastatic clear cell renal cell carcinoma (RCC). Methods: A systematic review with frequentist network meta-analysis (NMA) was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included randomized controlled trials (RCTs) investigating the use of: cabozantinib, pazopanib, sorafenib, sunitinib, tivozanib, cabozantinib + nivolumab, lenvat…

Liver Transplantation for Acute Liver Failure Following Regorafenib Treatment for Metastatic Gastrointestinal Stromal Tumor: Case Report and Literature Review.

Tyrosine kinase inhibitors (TKI) have improved survival in metastatic gastrointestinal stromal tumors (GIST) but can lead to drug-induced liver injury (DILI), rarely progressing to acute liver failure (ALF). We report the first documented case of regorafenib-induced ALF in a 51-year-old patient with metastatic ileal GIST, necessitating emergency liver transplantation (LT). The patient experienced prior hepatotoxicity with imatinib and disease progression under sunitinib. Following LT, sorafenib was initiated to treat peritoneal recurrence, and partial tumor control was achieved 3 years after t…

Precision therapeutic strategies for advanced gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs), the most common mesenchymal neoplasms of the gastrointestinal tract, are molecularly heterogeneous diseases rather than a single entity. Activating mutations in KIT and PDGFRA define the dominant biological dependencies and establish tyrosine kinase inhibition as a therapeutic backbone. Imatinib, followed by later-line tyrosine kinase inhibitors, including sunitinib, regorafenib, ripretinib, and genotype-selected avapritinib, have substantially prolonged survival. However, durable disease control remains limited by clonal evolution, most notably, polycl…

Converting lysosomes into photothermal organelles enables nanoparticle-free tumor ablation via intracellular vapor bubbles.

Photothermal nanomaterials enable precise tumor ablation but face limitations in biodistribution, tissue penetration, toxicity, and biodegra … em into transient endogenous nanosized photothermal reactors for subsequent light activation. Using sunitinib, a clinically approved lysosomotropic anticancer drug, and the commercially available dye LysoTracker Deep Red, lacking intrinsic anticancer activity, we demonstrate pulsed laser-induced VB formation from dye-enriched lysosomal compartments, leading …

Potent, Selective, and Drug-Like G Protein-Coupled Receptor Kinase 5 and 6 Inhibitors: Design, Synthesis, and X-Ray Structural Studies.

Herein, the design, synthesis, and evaluation of small molecules, drug-like G protein-coupled receptor kinase 5 (GRK5) inhibitors are reported. GRK5 has become an important drug development target against heart failure and cancer. GRK6, a close homolog of GRK5, is considered as a possible therapeutic target for multiple myeloma. A series of drug-like GRK5 inhibitors that form noncovalent interactions in the GRK5 active site are designed. In the design of these molecules, pyrroloindoline basic scaffold of sunitinib, an FDA-approved drug, is utilized and various N-heterocyclic carboxamides in th…

Late diagnosis of metastatic pheochromocytoma in multiple endocrine neoplasia 2B with rapid clinical decline.

Multiple endocrine neoplasia type 2B (MEN2B) is the rarest and most aggressive of the MEN syndromes. It is characterised by medullary thyroi … d lymphangitic spread of disease in the lungs. He unfortunately did not respond to a short trial of sunitinib and transitioned to comfort care.

Remarkable antitumor effect of nivolumab in a patient with metastatic renal cell carcinoma previously treated with a peptide-based vaccine.

INTRODUCTION: The safety and efficacy of combination therapy comprising immune checkpoint inhibitors and cancer-specific peptide vaccines have not yet been established. CASE PRESENTATION: A 71-year-old female metastatic renal cell carcinoma patient with multiple lung and pleural metastases. She had been treated with interferon alpha, sunitinib, axitinib, and pazopanib sequentially, but no clinical efficacy was observed. She participated in a clinical trial using cancer-specific peptide vaccine therapy. Initially no antitumor effect was observed, and vaccine therapy was ceased after two course…

Emerging therapies: angiogenesis inhibitors for ovarian cancer.

INTRODUCTION: Patients with epithelial ovarian cancer (EOC) have a high rate of recurrence, and overall survival remains at ∼ 25%. There is … pt, bevacizumab, cediranib, fosbretabulin, imatinib, nintedanib, pazopanib, saracatinib, sorafenib, sunitinib, and trebananib. EXPERT OPINION: These agents have particular rationale for potential use in EOC due to the molecular changes associated with EOC tumorigenesis, namely a significant increase in angiogenic activity. Due to the costs and toxicities a …

[Cardiovascular complications of chemotherapy].

In the last decades, oncological therapy has changed the natural history of many types of cancer, which can now be considered curable or as … s targeted agents (monoclonal antibody trastuzumab and bevacizumab and the tyrosin-kinase inhibitor sunitinib). Patient treated with chemotherapy are at higher risk of cardiovascular events than the general population, so that having undergone chemotherapy may be considered as a novel cardiovascular risk factor. This review briefly summarizes the most impor …

Everolimus in metastatic renal cell carcinoma: preliminary experience from Chang Gung Memorial Hospital.

BACKGROUND: Everolimus has been approved for second-line treatment of patients with metastatic renal cell carcinoma (mRCC) after failure of sorafenib or sunitinib. The purpose of this retrospective study was to assess the efficacy and safety of everolimus in Taiwanese patients with mRCC. METHODS: Between March 2009 and August 2011, 24 mRCC patients treated with everolimus were analyzed. Prior to everolimus, each patient had received therapy with at least one vascular endothelial growth factor receptor-tyrosine kinase inhibitor. Progression-free survival (PFS) and overall survival (OS) were es…

Medical treatment of recurrent meningiomas.

Meningiomas are the second most common primary brain tumor and are primarily treated with surgery (with or without embolization) and radioth … ays, such as somatostatin (Sandostatin(®) LAR, SOM230c), PDGF (imatinib), EGF (erlotinib) and VEGF (sunitinib and vatalanib). Early results using a targeted approach have been modest at best and are often associated with significant toxicity. Consequently and at present, the brain tumor guidelines recognize only three medical therapies for inoperable and ra …

[A Case of Giant Exophytic Gastric GIST Presenting with the Torricelli-Bernoulli Sign during Regorafenib Treatment].

Following surgery for rectal cancer and resection of the liver metastases, a giant gastric GIST was detected in an 81-yearold man during follow-up. Imatinib and sunitinib were administered; however, the tumor was refractory. Follow-up CT scans obtained while receiving regorafenib as third-line therapy revealed an increase in tumor size, and the disease was assessed as progressive (PD). At that time, a Torricelli-Bernoulli (T-B) sign was observed, indicating communication between the tumor interior and the gastric lumen. Reports of perforation during regorafenib administration are scarce, and t…

Solitary Clear Cell Renal Cell Carcinoma Metastasis to the Eyelid: A Case Report.

INTRODUCTION: This study is a case of solitary clear cell renal cell carcinoma (ccRCC) eyelid metastasis in a 66-year-old man as the first s … stopathology showed ccRCC. Postoperative examinations showed no signs of local or systemic disease. Sunitinib malate was administered to the patient. CONCLUSION: The eyelid metastasis in this case was still solitary and had been discovered before the existence of the primary tumor was known. Ocular metastasis of renal carcinoma is a rare initial manifestat …

The key m6A methylation regulator IGF2BP1 possesses potential prognostic value in papillary thyroid carcinoma.

Papillary thyroid carcinoma (PTC) poses a risk of recurrence, and the efficacy of existing treatments is limited. Consequently, there is an … c marker with high accuracy. Elevated IGF2BP1 also indicated greater sensitivity to doxorubicin and sunitinib. Clinically, low IGF2BP1 correlated with central lymph-node metastasis and BRAFV600E mutation. Additionally, IGF2BP1 overexpression suppresses thyroid carcinoma cell proliferation, invasion, and migration. In conclusion, High expression of IGF2BP1 w …

Targeting VEGFR-2 with piperazine bridged indolin-2-one derivatives.

As a key mediator of tumor angiogenesis, VEGFR-2 has emerged as a promising therapeutic target for combating cancer. In the present study, a series of 6-substituted-3-(4-(4-(substitutedphenyl/benzyl)piperazin-1-yl)benzylidene) indolin-2-one derivatives (2-24) were synthesized in good yields and structurally confirmed by IR, NMR, and HRMS analyses. Several compounds exhibited strong VEGFR-2 inhibition, with activities comparable to or exceeding that of sorafenib, but lower than sunitinib. Cytotoxicity assays against MCF-7 breast cancer cells revealed five derivatives (4, 7, 9, 10, and 12) more …

Metastatic tropism of molecularly defined clear-cell renal cell carcinoma clusters.

BACKGROUNDThe relationship between molecular subgroups in clear-cell renal cell carcinoma (ccRCC) and metastatic tropism is poorly understood.METHODSWe analyzed over 5,000 metastatic sites from 305 treatment-naive ccRCC patients in the IMmotion150 phase II clinical trial, where patients were randomized to atezolizumab, atezolizumab/bevacizumab, or sunitinib.RESULTSAngiogenic tumors (clusters 1 and 2) had a higher rate of pancreatic (21% vs. 6.9%; P = 0.002) and lower absolute number of lymph node (2.5 vs. 4.2; P = 0.006) metastases. In contrast, proliferative tumors (clusters 4 and 5) exhibite…

A Case of a Durable Partial Response to Late-Line Axitinib Following Prior Use of Tyrosine Kinase Inhibitors in Metastatic Papillary Renal Cell Carcinoma.

INTRODUCTION: Metastatic papillary renal cell carcinoma (PRCC) is associated with a poor prognosis. Many patients with PRCC respond to first … 0M1. He underwent left radical nephrectomy. The pathological diagnosis was PRCC type 2. After using sunitinib, cabozantinib, and nivolumab, axitinib was selected as fourth-line systemic therapy, resulting in a reduction in multiple liver metastases and 15 months of response. CONCLUSION: Late-sequence treatment with axitinib following prior use of tyrosine …

Диметилфумарат способствует разложению HNF1B и подавляет прогрессирование чистой почечной карциномы.

Чистая почечная карцинома (ccRCC) является самым смертельным подтипом рака почек, и его варианты лечения по-прежнему ограничены. Поэтому необходимо срочно найти лечебные агенты для лечения CCRCC. Здесь мы показываем, что диметилфумарат (ДМФ), одобренное лекарство от множественных склерозов [1] и псориаза, может сдерживать распространение клеток ЦКЦК. Механистически, гепатоцитовый ядерный фактор 1β (HNF1B), коэффициент транскрипции, ярко выраженный в CCRCC, поддерживается DMF в остатках цистейна, что ведет к его протеасомальной деградации. Кроме того, HNF1B взаимодействует с протеином, связанны

Совпадение в аннотации оригинала
Clear cell renal cell carcinoma (ccRCC) is the most lethal subtype of renal cancer, and its treatment options remain limited. Therefore, the … uppression of ccRCC cell proliferation. Importantly, oral administration of DMF sensitizes ccRCC to sunitinib treatment and enhances its efficacy in mice. In summary, we provide evidences supporting DMF as a potential drug for clinical treatment of ccRCC by targeting HNF1B and reveal a previously unrecognized role of HNF1B in regulating YAP in ccRCC.

In Vitro Cytotoxicity of Antiresorptive and Antiangiogenic Compounds on Oral Tissues Contributing to MRONJ: Systematic Review.

BACKGROUND: Invasive dental treatment in patients exposed to antiresorptive and antiangiogenic drugs can cause medication-related osteonecrosis of the jaw (MRONJ). Currently, the exact pathogenesis of this disease is unclear. METHODS: In March 2022, Medline (Ovid), Embase (Ovid), Scopus, and Web of Science were screened to identify eligible in vitro studies investigating the effects of antiresorptive and antiangiogenic compounds on orally derived cells. RESULTS: Fifty-nine articles met the inclusion criteria. Bisphosphonates were used in 57 studies, denosumab in two, and sunitinib and bevaci…

Engineered peptide-drug conjugate provides sustained protection of retinal ganglion cells with topical administration in rats.

Effective eye drop delivery systems for treating diseases of the posterior segment have yet to be clinically validated. Further, adherence to eye drop regimens is often problematic due to the difficulty and inconvenience of repetitive dosing. Here, we describe a strategy for topically dosing a peptide-drug conjugate to achieve effective and sustained therapeutic sunitinib concentrations to protect retinal ganglion cells (RGCs) in a rat model of optic nerve injury. We combined two promising delivery technologies, namely, a hypotonic gel-forming eye drop delivery system, and an engineered melani…