Mobile DNA, Год журнала: 2024, Номер 15(1)
Опубликована: Дек. 31, 2024
Язык: Английский
Cell Reports, Год журнала: 2025, Номер 44(1), С. 115206 - 115206
Опубликована: Янв. 1, 2025
Язык: Английский
Процитировано
6
Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)
Опубликована: Апрель 7, 2025
The cGAS-STING signaling pathway serves as a critical link between DNA sensing and innate immunity, has tremendous potential to improve anti-tumor immunity by generating type I interferons. However, STING agonists have shown decreasing biotherapeutic efficacy in clinical trials. Tumor metabolism, characterized aberrant nutrient utilization energy production, is fundamental hallmark of tumorigenesis. And modulating metabolic pathways tumor cells been discovered therapeutic strategy for tumors. As research concerning progressed, emerging evidence highlights its role reprogramming, independent immune function, indicating targets activation cancers. In this review, we delve into the interplay multiple pathways. We also synthesize current knowledge on antitumor functions STING, within microenvironment (TME) that could be exploited activation. This review necessity future dissect complex interactions with various cancer types, emphasizing personalized strategies based profiling.
Язык: Английский
Процитировано
1
Cell Death and Differentiation, Год журнала: 2024, Номер unknown
Опубликована: Окт. 23, 2024
Abstract By the time a tumor reaches clinical detectability, it contains around 10 8 –10 9 cells. However, during formation, significant cell loss occurs due to death. In some estimates, could take up thousand generations, over ~ 20-year life-span of tumor, reach which would correspond “theoretical” generation ~10 30 These rough calculations indicate that cancers are under negative selection. The fact they thrive implies “evolve”, and their evolutionary trajectories shaped by pressure environment. Evolvability cancer is function its heterogeneity, be at genetic, epigenetic, ecological/microenvironmental levels [1]. principles were summarized in proposed classification Evo (evolutionary) Eco (ecological) indexes used label index addresses cell-autonomous heterogeneity (genetic/epigenetic). describes ecological landscape (non-cell-autonomous) terms hazards survival resources available. reciprocal influence components critical, as can trigger self-sustaining loops shape evolvability [2]. Among various hallmarks [3], metabolic alterations appear unique intersect with both components. This partly because altered metabolism leads accumulation oncometabolites. oncometabolites have traditionally been viewed mediators non-cell-autonomous microenvironment. now increasingly recognized inducers genetic epigenetic modifications. Thus, uniquely positioned crossroads cancer. this review, mechanisms action will summarized, together roles phenotypic evolvability. An perspective impact on natural history presented.
Язык: Английский
Процитировано
5
Journal for ImmunoTherapy of Cancer, Год журнала: 2024, Номер 12(12), С. e009175 - e009175
Опубликована: Дек. 1, 2024
Glioma evolution is governed by a multitude of dynamic interactions between tumor cells and heterogenous neighboring, non-cancerous cells. This complex ecosystem, termed the microenvironment (TME), includes diverse immune cell types that have gained increasing attention for their critical paradoxical roles in control tumorigenesis. Recent work has revealed cellular composition functional state TME can evolve extensively depending on stage intrinsic features surrounding glioma Concurrently, adaptations to phenotype, including activation various states, occur context these alterations. In this review, we summarize important play key during each progression, from initiation escape, invasion recurrence. Understanding interplay development effective immunotherapies treatment.
Язык: Английский
Процитировано
4
American Journal Of Pathology, Год журнала: 2024, Номер unknown
Опубликована: Дек. 1, 2024
Язык: Английский
Процитировано
3
Current Oncology, Год журнала: 2025, Номер 32(1), С. 44 - 44
Опубликована: Янв. 17, 2025
Mutations in isocitrate dehydrogenase (IDH) genes are among the most frequently encountered molecular alterations cholangiocarcinoma (CCA). These neomorphic point mutations endow mutant IDH (mIDH) with ability to generate an R-enantiomer of 2-hydroxyglutarate (R2HG), a metabolite that drives malignant transformation through aberrant epigenetic signaling. As result, pharmacologic inhibition mIDH has become attractive therapeutic strategy CCAs harboring this mutation. One such inhibitor, ivosidenib, already undergone clinical validation and received FDA approval disease, but there is still much work be done improve outcomes CCA patients. In publication we will review pathogenesis treatment special emphasis on novel agents combinations currently under investigation.
Язык: Английский
Процитировано
0
Nature Cancer, Год журнала: 2025, Номер unknown
Опубликована: Янв. 17, 2025
Язык: Английский
Процитировано
0
Future Oncology, Год журнала: 2025, Номер unknown, С. 1 - 8
Опубликована: Март 3, 2025
Cholangiocarcinoma (CCA) is a rare and aggressive cancer with poor prognosis. Ivosidenib, an orally administered, first-in-class small-molecule inhibitor, targets the mutated isocitrate dehydrogenase 1 (IDH1) enzyme. Recently, ivosidenib has been approved for treating patients locally advanced or metastatic IDH1 R132-mutated CCA following at least one prior systemic therapy. The pivotal phase 3 ClarIDHy trial revealed that nearly doubled median progression-free survival significantly improved overall after adjusting crossover. However, prospective real-world data on remain limited. IDHIRA study prospective, multicenter, longitudinal, non-interventional conducted in Germany. will enroll 100 CCA, aiming to evaluate effectiveness, safety, quality of life (QoL) associated treatment patients.
Язык: Английский
Процитировано
0
Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, Год журнала: 2025, Номер 1871(5), С. 167769 - 167769
Опубликована: Март 5, 2025
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Март 3, 2025
Abstract Tumors with low expression of Interferon-Stimulated Genes (ISG) and Antigen Presentation (AP) genes respond relatively poorly to current immunotherapies. One the early hallmarks cancer is DNA hypomethylation in genomic repeat regions, resulting normally silenced endogenous “viral” elements. Such epigenetic changes have potential augment anti-tumor immune responses as well reduce tumor cell fitness through generation aberrant nucleic acid species (NAS) consequent activation NAS-sensing pathways. Therefore, evolution should favor additional selective events that suppress NAS generation, possibly yielding specific therapeutic vulnerabilities. Here, we show Lysine Demethylase 5 (KDM5) family regulatory enzymes R-loop formation regions cells. We find KDM5 inhibition luminal breast cells results R-loop-mediated damage, reduced an increase ISG AP signatures surface Major Histocompatibility Complex (MHC) class I, mediated by RNA:DNA hybrid CGAS/STING pathway. does not result damage or pathway normal epithelial cells, suggesting inhibitors may enable a wide window this setting, compared STING agonists Type I Interferons. These findings provide new insights into interplay between regulation repeats, formation, innate immunity, context vulnerability.
Язык: Английский
Процитировано
0