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The drug response sensitivity and related prognosis of prostate cancer varied from races, while the original mechanism remains rarely understood. In this study, the comprehensive signature including transcriptomics, epigenome and single nucleotide polymorphisms (SNPs) of 485 PCa cases- including 415 Whites, 58 Blacks and 12 Asians from the TCGA database were analyzed to investigate the drug metabolism differences between races. We found that Blacks and Whites had a more prominent drug metabolism, cytotoxic therapy resistance, and endocrine therapy resistance than Asians, while Whites were more prominent in drug metabolism, cytotoxic therapy resistance and endocrine therapy resistance than Blacks. Subsequently, the targeted regulation analysis indicated that the racial differences in cytotoxic therapy resistance, endocrine therapy resistance, might originate from drug metabolisms, and 19 drug metabolism-related core genes were confirmed in the multi-omics network for subsequent analysis. Furthermore, we verified that significantly affected antineoplastic drugs sensitivities in PCa cell lines, and these genes also showed good predictive efficiency of drug response and treatment outcomes for PCa in this cohort of patients. These findings revealed a comprehensive signature of drug metabolism differences for the Whites, Blacks and Asians, and it may provide some evidence for making individualized treatment strategies.
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http://dx.doi.org/10.18632/aging.203158 | DOI Listing |
J Environ Pathol Toxicol Oncol
January 2025
Department of Pharmacy, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China.
Despite advancements in systemic therapy, the mortality rate for patients with metastatic melanoma remains around 70%, underscoring the imperative for alternative treatment strategies. Through the establishment of a chemoresistant melanoma model and a subsequent drug investigation, we have identified pacritinib, a medication designed for treating myelofibrosis and severe thrombocytopenia, as a potential candidate to overcome resistance to melanoma therapy. Our research reveals that pacritinib, administered at clinically achievable concentrations, effectively targets dacarbazine-resistant melanoma cells by suppressing IRAK1 rather than JAK2.
View Article and Find Full Text PDFJ Med Chem
September 2025
State Key Laboratory of Bioactive Molecules and Druggability Assessment, Guangdong Basic Research Center of Excellence for Natural Bioactive Molecules and Discovery of Innovative Drugs, International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery o
Aberrant activation of fibroblast growth factor receptors (FGFRs) plays a critical role in tumorigenesis across multiple cancer types, driving the development of various FGFR inhibitors. Despite clinical advances, therapeutic efficacy remains limited by the emergence of drug resistance, primarily mediated by gatekeeper mutations in FGFRs. To overcome this challenge, we designed and synthesized a novel series of 7-(1-methyl-1-indole-3-yl)-5-pyrrolo[2,3-]pyrazine derivatives as covalent pan-FGFR inhibitors targeting both wild-type and gatekeeper mutants.
View Article and Find Full Text PDFJ Med Chem
September 2025
Faculty of Mathematics and Natural Sciences, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich Heine University Düsseldorf, 40225 Düsseldorf, Germany.
New treatment strategies are required to combat the spread of drug-resistant malaria. The synthesis and preclinical evaluation of novel 3-hydroxy-propanamidines (HPAs), with modifications of the phenanthrene and the 4-fluorobenzamidine moieties, has yielded several analogs exhibiting excellent in vitro growth inhibition of drug-sensitive or resistant fresh clinical isolates and culture-adapted strains. No cytotoxicity in the human HepG2 cell line was observed, demonstrating notable parasite selectivity.
View Article and Find Full Text PDFChem Biodivers
September 2025
Department of Chemistry, Govt. Raza P.G. College, Rampur, India.
Parasitic diseases continue to be a major public health burden, particularly in low- and middle-income countries. With the emergence of drug-resistant strains and limitations of current therapies, there is a growing interest in natural products as alternative treatment options. Coumarins, a diverse class of plant-derived secondary metabolites, have shown significant potential as antiparasitic agents.
View Article and Find Full Text PDFRev Esc Enferm USP
September 2025
Universidade de São Paulo, Escola de Enfermagem, São Paulo, SP, Brazil.
Objective: To identify pregnant women with urinary tract infections who are being monitored at a primary health care unit and their knowledge about antibiotics, as well as facilitating and challenging factors perceived by nurses that influence care, with a focus on antimicrobial resistance.
Method: Exploratory, descriptive study with a quantitative approach, involving pregnant women with urinary tract infections undergoing antibiotic treatment at a municipal health unit in São Paulo and nurses working at the same location. Data were obtained from computerized systems, medical records, and interviews, and were synthesized and analyzed using Microsoft Excel and Stata software.