Annals of Medicine, Год журнала: 2025, Номер 57(1)
Опубликована: Янв. 13, 2025
Background We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, found significant differences pyrimidine metabolites. The PMGs is associated with clinical prognosis several cancers, but its biological role PCa still unclear.
Язык: Английский
International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2652 - 2652
Опубликована: Янв. 31, 2023
Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related deaths in world. Metabolic reprogramming considered a new hallmark cancer, but it remains unclearly described HCC. The dysregulation PI3K/AKT/mTOR signaling pathway common HCC and is, therefore, topic further research concern developing novel target for liver cancer therapy. In this review, we illustrate mechanisms by which network accountable regulating cellular metabolism, including glucose lipid amino acid pyrimidine oxidative summarize ongoing clinical trials based on inhibition
Язык: Английский
Процитировано
123
Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)
Опубликована: Май 27, 2024
Notch signaling, renowned for its role in regulating cell fate, organ development, and tissue homeostasis across metazoans, is highly conserved throughout evolution. The receptor ligands are transmembrane proteins containing epidermal growth factor-like repeat sequences, typically necessitating receptor-ligand interaction to initiate classical signaling transduction. Accumulating evidence indicates that the pathway serves as both an oncogenic factor a tumor suppressor various cancer types. Dysregulation of this promotes epithelial-mesenchymal transition angiogenesis malignancies, closely linked proliferation, invasion, metastasis. Furthermore, contributes maintaining stem-like properties cells, thereby enhancing invasiveness. regulatory metabolic reprogramming microenvironment suggests pivotal involvement balancing suppressive effects. Moreover, implicated conferring chemoresistance cells. Therefore, comprehensive understanding these biological processes crucial developing innovative therapeutic strategies targeting signaling. This review focuses on research progress cancers, providing in-depth insights into potential mechanisms regulation occurrence progression cancer. Additionally, summarizes pharmaceutical clinical trials therapy, aiming offer new human malignancies.
Язык: Английский
Процитировано
81
Trends in Cell Biology, Год журнала: 2023, Номер 33(11), С. 950 - 966
Опубликована: Март 24, 2023
Язык: Английский
Процитировано
44
Nature Communications, Год журнала: 2025, Номер 16(1)
Опубликована: Янв. 2, 2025
Colorectal cancer (CRC) is stratified into four consensus molecular subtypes (CMS1-4). CMS3 represents the metabolic subtype, but its wiring remains largely undefined. To identify underlying tumorigenesis of CMS3, organoids derived from 16 genetically engineered mouse models are analyzed. Upon in vitro Cre-recombinase activation, transformation established and transcriptional profiling reveals that distinct CMSs (CMS2-4) modeled with different organoids. CMS3-like, signature-positive, induced by KRAS mutations. Interestingly, signatures subsequently shown to result enterocyte-like differentiation both human cancers. Further analysis carbamoyl-phosphate synthase 1 (CPS1) sucrase-isomaltase (SI) as signature proteins. More importantly, CPS1 crucial for de novo pyrimidine synthesis inhibition targets proliferation stemness, facilitating differentiation, while CMS2 CMS4 not affected. Our data point an CRCs reveal a selective vulnerability this subtype through inhibition.
Язык: Английский
Процитировано
2
BMC Microbiology, Год журнала: 2022, Номер 22(1)
Опубликована: Фев. 25, 2022
Abstract Background The microbiome alterations are associated with cancer growth and may influence the immune system response to therapy. Particularly, gut has been recently shown modulate melanoma immunotherapy. However, role of skin not well explored in tumour microenvironment link between investigated progression. Therefore, aim present study was examine associations dysbiosis using MeLiM porcine model progression spontaneous regression. Results Parallel analysis cutaneous microbiota faecal same individuals performed 8 12 weeks old piglets. bacterial composition samples analysed by high throughput sequencing V4-V5 region 16S rRNA gene. A significant difference diversity richness tissue healthy piglets control were observed. Both Principal Coordinate Analysis Non-metric multidimensional scaling revealed dissimilarities different communities. Linear discriminant effect size at genus level determined potential biomarkers multiple Lactobacillus, Clostridium sensu stricto 1 Corynebacterium most discriminately higher genera microbiome, while Fusobacterium, Trueperella, Staphylococcus, Streptococcus Bacteroides abundant microbiome. Bacteroides, Fusobacterium Escherichia-Shigella Potential functional pathways based on KEGG database indicated differences predicted profile metabolisms enriched genes related membrane transports allowing for increase intestinal permeability alteration mucosal barrier. Conclusion as identified. provide promising information further studies local involvement support development new therapeutic approaches.
Язык: Английский
Процитировано
67
Cells, Год журнала: 2022, Номер 11(4), С. 739 - 739
Опубликована: Фев. 20, 2022
Nucleotides are synthesized through two distinct pathways: de novo synthesis and nucleoside salvage. Whereas the pathway synthesizes nucleotides from amino acids glucose, salvage recovers nucleosides or bases formed during DNA RNA degradation. In contrast to high proliferating non-malignant cells, which highly dependent on synthesis, cancer cells can switch pathways maintain efficient replication. Pyrimidine remains target of interest in therapy several inhibitors showed promising results vivo models. 1980s 1990s, poor responses were however observed clinical trials with currently existing pyrimidine inhibitors. To overcome limitations trials, targeting alone combination was suggested. Even though this approach initially results, it received fresh attention only recently. Here we discuss re-discovery for replication commonly used antimetabolites various preclinical models trials. We also highlight newly emerged targets as well a immunotherapy.
Язык: Английский
Процитировано
43
Pharmacology & Therapeutics, Год журнала: 2022, Номер 237, С. 108256 - 108256
Опубликована: Июль 25, 2022
Язык: Английский
Процитировано
38
International Journal of Biological Sciences, Год журнала: 2023, Номер 19(3), С. 811 - 828
Опубликована: Янв. 1, 2023
Currently, cancer treatment mainly consists of surgery, radiotherapy, chemotherapy, immunotherapy, and molecular targeted therapy, which radiotherapy is one the major pillars.However, occurrence radioresistance largely limits its therapeutic effect.Metabolic reprogramming an important hallmark in progression resistance.In DNA breakage mechanism cell damage, turn, cells are prone to increase metabolic flux glucose, glutamine, serine, arginine, fatty acids etc., thus providing sufficient substrates energy for damage repair.Therefore, studying linkage between may provide new ideas improving efficacy tumor therapy.This review focuses on role alterations, including amino acid, lipid, nucleotide other ion metabolism, radioresistance, proposes possible targets improve radiotherapy.
Язык: Английский
Процитировано
23
Molecules, Год журнала: 2024, Номер 29(3), С. 635 - 635
Опубликована: Янв. 29, 2024
Repurposing is a universal mechanism for innovation, from the evolution of feathers to invention Velcro tape. particularly attractive drug development, given that it costs more than billion dollars and takes longer ten years make new scratch. The COVID-19 pandemic has triggered large number repurposing activities. At same time, highlighted potential pitfalls, in particular when concessions are made target product profile. Here, we discuss pros cons infectious diseases analyze different ways repurposing. We distinguish between opportunistic rational approaches, i.e., just saving time money by screening compounds already approved versus based on common pathogens. latter can be further distinguished into divergent convergent: points attack share ancestry (e.g., prokaryotic targets apicoplast malaria parasites), whereas those convergent arise shared lifestyle susceptibility bacteria, parasites, tumor cells antifolates due their high rate DNA synthesis). illustrate how such scenarios capitalized using examples drugs have been repurposed to, from, or within field anti-infective chemotherapy.
Язык: Английский
Процитировано
8
Cell Reports, Год журнала: 2025, Номер 44(1), С. 115179 - 115179
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
1