ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 1824 - 1825
Published: Oct. 29, 2024
Provided herein are novel bicyclic ureas as JAK2 inhibitors, pharmaceutical compositions, use of such compounds in treating hematological cancer, and processes for preparing compounds.
Language: Английский
International Journal of Genomics, Journal Year: 2025, Volume and Issue: 2025(1)
Published: Jan. 1, 2025
Background: Recently, exportin gene family members have been demonstrated to play essential roles in tumor progression. However, research on the clinical significance of is limited clear cell renal carcinoma (ccRCC). Methods: Pan-cancer data, ccRCC multiomics and single-cell sequence were included analyze differences DNA methylation modification, single nucleotide variations (SNVs), copy number (CNVs), expression levels members. Non-negative matrix factorization was used identify molecular subtypes based members, prognostic biological different compared across multiple dimensions. Results: Exportin upregulated pan-cancer expression, their aberrant significantly influenced by methylation, SNV, CNV, particularly ccRCC. Based two subtypes, famliy genes (XPO)-based subtype 1 (XPS1) 2 (XPS2), identified. The XPS2 higher than those XPS1, prognosis poorer. had lower immune component abundance exhaustion scores. Its response rate immunotherapy that XPS1 subtype, but it more sensitive small molecules, including mercaptopurine nutlin. Among them, exportin-1 (XPO1) a potential diagnostic therapeutic target for ccRCC, which can promote cancer progression activating PI3K-AKT-mTOR (phosphatidylinositol 3-kinase (PI3K)/AKT serine/threonine kinase (AKT)/mechanistic rapamycin (MTOR)) interferon alpha pathways. Conclusion: This study analyzed at level identified distinct guide personalized management patients.
Language: Английский
Citations
0
Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)
Published: May 23, 2025
Renal cell carcinoma (RCC) is a highly malignant tumor with poor prognosis, underscoring the urgent need for novel therapeutic strategies. RCC cells exhibit rapid proliferation and high metabolic demands, leading to hypoglycemic hypoxic conditions within microenvironment (TME). Our study reveals that fructose transporter Glut5 prominently expressed in RCC, facilitating increased uptake. This compensatory mechanism supports survival under glucose deprivation hypoxia. Fructose utilization sustains proliferation, migration, colony formation vitro, significantly reduces apoptosis, accelerates renal cancer growth vivo. Mechanistically, activates cAMP/PKA signaling pathway, driving reprogramming promoting progression. Furthermore, 2,5-dehydro-D-mannitol (2,5-AM), competitive inhibitor of transport, inhibits both vivo vitro. These findings provide new insights into role metabolism progression suggest potential targets.
Language: Английский
Citations
0
Cell Death and Disease, Journal Year: 2025, Volume and Issue: 16(1)
Published: April 24, 2025
Abstract Metastasis remains a significant challenge in the management of clear cell renal carcinoma (ccRCC), and continued focus on its underlying mechanisms is crucial for improving patient outcomes optimizing clinical therapies. The ovarian-tumor related protease (OTU) involved regulating critical signaling pathways, but functions most OTUs have yet to be explored. In this study, an unbiased RNAi screening revealed that ovarian tumor domain-containing 2 (YOD1) knockdown significantly promoted metastasis. YOD1 downregulation ccRCC growth metastasis both vitro vivo. Notably, stimulated organoids derived from patients. Further investigation directly interacted with stabilized Zinc finger protein 24 (ZNF24) expression by deubiquitination manner dependent catalytic activity. inhibition attenuated ZNF24 transcriptional repression vascular endothelial factor A (VEGFA), thereby promoting VEGFA gene expression. Furthermore, was identified as key mediator function. downregulated tissues, strong correlation between them. Importantly, reduced levels were strongly associated poor Our results reveal mechanism which regulates transcription suppresses tumorigenesis deubiquitinating ZNF24, providing therapeutic target ccRCC.
Language: Английский
Citations
0
Biomedicines, Journal Year: 2024, Volume and Issue: 12(10), P. 2171 - 2171
Published: Sept. 24, 2024
Background: Cancer stem-like cells (CSCs), a distinct subset recognized for their stem cell-like abilities, are intimately linked to the resistance radiotherapy, metastatic behaviors, and self-renewal capacities in tumors. Despite relevance, definitive traits importance of CSCs realm oncology still not fully comprehended, particularly context clear cell renal carcinoma (ccRCC). A comprehensive understanding these CSCs’ properties relation stemness, impact on efficacy treatment medication, is paramount importance. Methods: In meticulous research effort, we have identified new molecular categories designated as CRCS1 CRCS2 through application an unsupervised clustering algorithm. The analysis subtypes included examination tumor immune environment, patterns metabolic activity, progression disease, its response immunotherapy. addition, delved into subtypes’ distinctive clinical presentations, landscape genomic alterations, likelihood various pharmacological interventions. Proceeding from insights, prognostic models were developed that could potentially forecast outcomes patients with ccRCC, well inform strategies surveillance recurrence after handling drug-resistant scenarios. Results: Compared CRCS1, had lower stage/grading better prognosis. subtype was hypoxic state characterized by suppression exclusion function, which sensitive gefitinib, erlotinib, saracatinib. constructed risk model performed both training validation cohorts, helping identify who may benefit specific treatments or at drug resistance. novel therapeutic target, SAA2, regulating neutrophil fibroblast infiltration, and, thus promoting ccRCC progression, identified. Conclusions: Our findings highlight key role shaping microenvironment, crucial therapy guidance. Recognizing stemness helps predict efficacy, recurrence, resistance, informing enhancing patient outcomes.
Language: Английский
Citations
2
Seminars in Oncology Nursing, Journal Year: 2024, Volume and Issue: unknown, P. 151743 - 151743
Published: Oct. 1, 2024
Language: Английский
Citations
0
ACS Medicinal Chemistry Letters, Journal Year: 2024, Volume and Issue: 15(11), P. 1824 - 1825
Published: Oct. 29, 2024
Provided herein are novel bicyclic ureas as JAK2 inhibitors, pharmaceutical compositions, use of such compounds in treating hematological cancer, and processes for preparing compounds.
Language: Английский
Citations
0