Epigenetics-targeted drugs: current paradigms and future challenges

Signal Transduction and Targeted Therapy, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 26, 2024

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone RNA remodeling, and non-coding regulation. These mechanisms their associated enzymes convey genetic information independently of base sequences, playing essential roles in organismal development homeostasis. Conversely, disruptions epigenetic landscapes critically influence the pathogenesis various human diseases. This understanding has laid robust theoretical groundwork for developing drugs that target epigenetics-modifying pathological conditions. Over past two decades, growing array small molecule targeting such as methyltransferase, deacetylase, isocitrate dehydrogenase, enhancer zeste homolog 2, have been thoroughly investigated implemented therapeutic options, particularly oncology. Additionally, numerous epigenetics-targeted are undergoing clinical trials, offering promising prospects benefits. review delineates epigenetics physiological contexts underscores pioneering studies on discovery implementation drugs. include inhibitors, agonists, degraders, multitarget agents, aiming to identify practical challenges avenues future research. Ultimately, this aims deepen epigenetics-oriented strategies further application settings.

Язык: Английский

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Advancements in clinical RNA therapeutics: Present developments and prospective outlooks

Cell Reports Medicine, Год журнала: 2024, Номер 5(5), С. 101555 - 101555

Опубликована: Май 1, 2024

RNA molecules have emerged as promising clinical therapeutics due to their ability target "undruggable" proteins or with high precision and minimal side effects. Nevertheless, the primary challenge in lies rapid degradation clearance from systemic circulation, inability traverse cell membranes, efficient intracellular delivery of bioactive molecules. In this review, we explore implications RNAs diseases provide a chronological overview development therapeutics. Additionally, summarize technological advances RNA-screening design, encompassing various databases design platforms. The paper then presents an update on FDA-approved those currently undergoing trials for diseases, specific emphasis medicine vaccines.

Язык: Английский

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Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer

Nanoscale, Год журнала: 2024, Номер 16(8), С. 3881 - 3914

Опубликована: Янв. 1, 2024

The long noncoding RNAs (lncRNAs) comprise a wide range of RNA species whose length exceeds 200 nucleotides, which regulate the expression genes and cellular functions in organisms.

Язык: Английский

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TCL1A in naïve B cells as a therapeutic target for type 1 diabetes

EBioMedicine, Год журнала: 2025, Номер 113, С. 105593 - 105593

Опубликована: Фев. 12, 2025

Язык: Английский

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Liquid-liquid phase separation-related lncRNA prognostic signature and ZNF32-AS2 as a novel biomarker in hepatocellular carcinoma

Computers in Biology and Medicine, Год журнала: 2024, Номер 169, С. 107975 - 107975

Опубликована: Янв. 6, 2024

Liquid-liquid phase separation (LLPS) enhances oncogenic signaling pathways and advances cancer progression, has been proposed as a promising biomarker intervention target. Nevertheless, doubts remain about the prognostic importance of LLPS-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). Methods: An lncRNA signature was generated by drivers regulators LLPS, validated external datasets. The underlying genetic changes functional enrichment were assessed. drug sensitivity response to immunotherapy predicted patients categorized high-risk low-risk. Clinical samples, agonist, dispersant used identify lncRNAs with most significant expression change. Cancer cells ZNF32-AS2 regulation subjected colony formation assay, scratch test migration invasion sorafenib resistance xenograft tumor model. Results: hub identified through Weighted Gene Co-Expression Network Analysis showed outstanding performance training validation cohorts consistently, molecular characteristics varied between different risk groups. Potential drugs for individuals identified, low-risk demonstrated more favorable reaction immunotherapy. change agonist treatment. promoted proliferation, mobility, liver cells. Conclusions: may help assess prognosis predict treatment efficacy clinical settings. cells, be novel potential carcinoma.

Язык: Английский

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Long Non-Coding RNAs in Ovarian Cancer: Mechanistic Insights and Clinical Applications

Cancers, Год журнала: 2025, Номер 17(3), С. 472 - 472

Опубликована: Янв. 30, 2025

Background/Objectives: Ovarian cancer is a leading cause of gynecological mortality worldwide, often diagnosed at advanced stages due to vague symptoms and the lack effective early detection methods. Long non-coding RNAs (lncRNAs) have emerged as key regulators in biology, influencing cellular processes such proliferation, apoptosis, chemoresistance. This review explores multifaceted roles lncRNAs ovarian pathogenesis their potential biomarkers therapeutic targets. Methods: A comprehensive literature was conducted analyze structural functional characteristics contributions biology. includes regulatory mechanisms, interactions with signaling pathways, implications for resistance. Advanced bioinformatics omics approaches were also evaluated lncRNA research. Results: The highlights dual role oncogenes tumor suppressors, modulating cell invasion, angiogenesis. Specific lncRNAs, HOTAIR GAS5, demonstrate significant diagnostic Emerging technologies, single-cell sequencing, provide valuable insights into microenvironment heterogeneity expression. Conclusions: LncRNAs hold transformative advancing diagnosis, prognosis, treatment. Targeting or associated pathways offers promising strategies overcome therapy resistance enhance personalized medicine. Continued research integrating will be essential unlock full clinical management.

Язык: Английский

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Disease‐Associated Risk Variants and Expression Levels of the lncRNA, CDKN2B‐AS1, Are Associated With the Progression of HCC

Journal of Cellular and Molecular Medicine, Год журнала: 2025, Номер 29(6)

Опубликована: Март 1, 2025

ABSTRACT The most susceptible loci of hepatocellular carcinoma (HCC) identified by genome‐wide association studies are located in non‐coding regions. antisense RNA at the INK4 locus (ANRIL), also known as cyclin‐dependent kinase inhibitor 2B 1 (CDKN2B‐AS1), is a long (lnc)RNA situated within and to genes encoding CDKN2A/B on chromosome 9p21.3. Single‐nucleotide polymorphisms (SNPs) CDKN2B‐AS1 associated with several cancer types, but their impacts HCC remain unclear. In this study, we investigated effects SNPs both susceptibility its clinicopathological development. Five SNP loci—rs564398 (T/C), rs1333048 (A/C), rs1537373 (G/T), rs2151280 (A/G) rs8181047 (G/A)—were analysed using TaqMan allelic discrimination assay for genotyping cohort 810 patients 1190 healthy controls. Under dominant model, least one minor C‐allele rs564398 showed lower risk liver cirrhosis (odds ratio (OR) = 0.677). Additionally, GT + TT genotype had reduced developing large tumours (T3 T4) advanced clinical stages (III/IV), particularly male population (OR 0.644 0.679). Furthermore, data from Cancer Genome Atlas revealed that expression levels were elevated tissues compared normal correlated T stages, high histological grades poor prognoses. Our findings suggest polymorphic variants may influence development progression Taiwanese population.

Язык: Английский

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Current Research in Drug-Free Cancer Therapies

Bioengineering, Год журнала: 2025, Номер 12(4), С. 341 - 341

Опубликована: Март 26, 2025

Cancer treatment has historically depended on conventional methods like chemotherapy, radiation, and surgery; however, these strategies frequently present considerable limitations, including toxicity, resistance, negative impacts healthy tissues. In addressing challenges, drug-free cancer therapies have developed as viable alternatives, utilizing advanced physical biological to specifically target tumor cells while reducing damage normal This review examines several strategies, such high-intensity focused energy beams, nanosecond pulsed electric fields, photothermal therapy well the use of inorganic nanoparticles promote selective apoptosis. We also investigate significance targeting microenvironment, precision medicine, immunotherapy in progression personalized therapies. Although approaches demonstrate significant promise, challenges scalability, safety, regulatory obstacles must be resolved for clinical application. paper presents an overview current research therapies, emphasizing recent advancements, underlying scientific principles, steps required implementation.

Язык: Английский

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Deciphering the mysteries of MEG3 LncRNA and its implications in genitourinary cancers

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Апрель 2, 2025

Maternally expressed gene 3 (MEG3), a long non-coding RNA, plays pivotal role in various biological processes, including tumorigenesis. Aberrant expression of MEG3 has been implicated several cancers, genitourinary malignancies. This comprehensive review explores the multifaceted functions context cancers through unravelling molecular mechanisms underlying influence on cellular proliferation, apoptosis, invasion, and metastasis. Additionally, we discuss potential clinical implications as biomarker therapeutic target cancers. By unraveling intricate these this aims to contribute development novel strategies for diagnosis treatment

Язык: Английский

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Neoadjuvant Chemotherapy With Cisplatin Up‐Regulates GSDMD to Enhance Oral Squamous Cell Carcinoma Metastasis Through MMP14‐Mediated EMT Activation

Advanced Science, Год журнала: 2025, Номер unknown

Опубликована: Апрель 3, 2025

Neoadjuvant chemotherapy has been widely used for the treatment of solid tumors. However, clinical observations have shown that patients with oral squamous cell carcinoma (OSCC) who are receiving neoadjuvant cisplatin still face issues such as a poor lymph node response and even progression, but underlying mechanisms remain unidentified. In this work, it is found low-dose promoted migration, invasion metastasis, gasdermin D (GSDMD) identified potential regulator. GSDMD interacted MMP14, promoting its expression epithelial‒mesenchymal transition (EMT) activation without activating pyroptosis. Moreover, pH-responsive nanoparticles (NPs) systemic delivery siRNA (siGSDMD) developed showed NP-delivered siGSDMD can effectively inhibit OSCC tumor growth metastasis via efficient silencing in vivo. This findings indicate be biomarker to predict prognosis NP-mediated promising strategy advanced cisplatin.

Язык: Английский

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