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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Metabolic and epigenetic regulation of macrophage polarization in atherosclerosis: molecular mechanisms and targeted therapies

Pharmacological Research, Год журнала: 2025, Номер 212, С. 107588 - 107588

Опубликована: Янв. 7, 2025

Atherosclerosis, a multifactorial progressive inflammatory disease, is the common pathology underlying cardiovascular and cerebrovascular diseases. The macrophage plasticity involved in pathogenesis of atherosclerosis. With advance metabolomics epigenetics, metabolites/metabolic epigenetic modification such as DNA methylation, histone noncoding RNA, play crucial role polarization progression Herein, we provide comprehensive review essential metabolic regulation, well crosstalk between two regulating We also highlight potential therapeutic strategies via modifications for atherosclerosis, offer recommendations to our knowledge roles metabolic-epigenetic context Fundamental studies that elucidate mechanisms by which regulation influence atherosclerosis will pave way novel approaches.

Язык: Английский

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Utilizing 4-Sulfonylcalix[4]arene as a Selective Mobile Phase Additive for the Capture of Methylated Peptides

Analytical Chemistry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 26, 2025

Protein methylation has attracted increasing attention due to its significant regulatory roles in various biological processes. However, the diversity of forms, subtle differences between methylated and nonmodified sites, their ultralow abundances pose substantial challenges for capturing isolating peptides from samples. Herein, we develop a chromatographic method that utilizes 4-sulfonylcalix[4]arene (SC4A) as mobile phase additive Click-Maltose stationary separate methylated/nonmethylated through adsorption SC4A-K(Me3) complex. By utilization interaction calix[4]arene cavities trimethylated lysine residues, could be specifically separated peptide This significantly improves signal-to-noise ratio (S/N), even samples containing 10-fold excess bovine serum albumin (BSA) trypsin digests. Additionally, successfully enriched 12 histone study paves way selective enrichment post-translational modification proteomics (PTMs), enhancing both capture efficiency selectivity providing robust technical support subsequent research.

Язык: Английский

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Plasma Cell-Free Tumor Methylome as a Biomarker in Solid Tumors: Biology and Applications

Current Oncology, Год журнала: 2024, Номер 31(1), С. 482 - 500

Опубликована: Янв. 13, 2024

DNA methylation is a fundamental mechanism of epigenetic control in cells and its dysregulation strongly implicated cancer development. Cancers possess an extensively hypomethylated genome with focal regions hypermethylation at CPG islands. Due to the highly conserved nature cancer-specific methylation, detection cell-free plasma using liquid biopsies constitutes area interest biomarker research. The advent next-generation sequencing newer computational technologies have allowed for development diagnostic prognostic biomarkers that utilize profiling diagnose disease stratify risk. Methylome-based predictive can determine response anti-cancer therapy. An additional emerging application these minimal residual monitoring. Several key challenges need be addressed before cfDNA-based become fully integrated into practice. first relates biology stability cfDNA. second concerns clinical validity generalizability methylation-based assays, many which are type-specific. third involves their practicability, stumbling block translating from bench clinic. Future work on developing pan-cancer assays respective validities confirmed well-designed, prospective trials crucial pushing greater use tools oncology.

Язык: Английский

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OTUD4 promotes the progression of glioblastoma by deubiquitinating CDK1 and activating MAPK signaling pathway

Cell Death and Disease, Год журнала: 2024, Номер 15(3)

Опубликована: Март 1, 2024

Abstract Glioblastoma, IDH-Wild type (GBM, CNS WHO Grade 4) is a highly heterogeneous and aggressive primary malignant brain tumor with high morbidity, mortality, poor patient prognosis. The global burden of GBM increasing notably due to limited treatment options, drug delivery problems, the lack characteristic molecular targets. OTU deubiquitinase 4 (OTUD4) potential predictive factor for several cancers such as breast cancer, liver lung cancer. However, its function in remains unknown. In this study, we found that expression OTUD4 positively associated prognosis patients. Moreover, provided vitro vivo evidence promotes proliferation invasion cells. Mechanism studies showed that, on one hand, directly interacts cyclin-dependent kinase 1 (CDK1) stabilizes CDK1 by removing K11, K29, K33-linked polyubiquitination. On other binds fibroblast growth receptor (FGFR1) reduces FGFR1’s K6 K27-linked polyubiquitination, thereby indirectly stabilizing CDK1, ultimately influencing activation downstream MAPK signaling pathway. Collectively, our results revealed progression via OTUD4-CDK1-MAPK axis, may be prospective therapeutic target treatment.

Язык: Английский

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Enhancing siRNA efficacy in vivo with extended nucleic acid backbones

Nature Biotechnology, Год журнала: 2024, Номер unknown

Опубликована: Авг. 1, 2024

Язык: Английский

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Biological function molecular pathways and druggability of DNMT2/TRDMT1

Pharmacological Research, Год журнала: 2024, Номер 205, С. 107222 - 107222

Опубликована: Май 21, 2024

5-methylcytosine (m

Язык: Английский

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Oxidative stress-mediated epigenetic remodeling, metastatic progression and cell signaling in cancer

ONCOLOGIE, Год журнала: 2024, Номер 26(4), С. 493 - 507

Опубликована: Июль 1, 2024

Язык: Английский

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Implication of protein post translational modifications in gastric cancer

Frontiers in Cell and Developmental Biology, Год журнала: 2025, Номер 13

Опубликована: Фев. 4, 2025

Gastric cancer (GC) is one of the most common and highly lethal malignant tumors worldwide, its occurrence development are regulated by multiple molecular mechanisms. Post-translational modifications (PTM) forms include ubiquitylation, phosphorylation, acetylation methylation. Emerging research has highlighted lactylation glycosylation. The diverse realm PTM crosstalk linked to many critical signaling events involved in neoplastic transformation, carcinogenesis metastasis. This review provides a comprehensive overview impact on progression GC. Specifically, aberrant have been shown alter proliferation, migration, invasion capabilities GC cells. Moreover, closely associated with resistance chemotherapeutic agents Notably, this also discusses phenomenon crosstalk, highlighting interactions among their roles regulating pathways protein functions. Therefore, in-depth investigation into mechanisms targeted therapeutic strategies hold promise for advancing early diagnosis, treatment, prognostic evaluation GC, offering novel insights future directions.

Язык: Английский

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Unlocking Longevity in Aesthetic Dermatology: Epigenetics, Aging, and Personalized Care

International Journal of Dermatology, Год журнала: 2025, Номер unknown

Опубликована: Март 10, 2025

ABSTRACT The concept of aging has evolved from being primarily attributed to genetic factors recognizing the critical role epigenetic mechanisms. Recent advancements, such as clocks, have provided tools assess biological age and offer insights into processes at molecular level. In aesthetic dermatology, understanding these allows for more personalized, effective interventions targeting root causes skin aging. This review explores interplay changes, aging, potential personalized care enhance longevity rejuvenation. is based on an extensive literature search conducted across PubMed other scientific databases. Studies focused mechanisms DNA methylation, histone modifications, their relationship Particular attention was given recent advancements in including Horvath's Clock GrimAge, implications dermatological treatments. Epigenetic Clock, demonstrated utility assessing through methylation markers, revealing actionable processes. Energy‐based devices like fractional lasers radiofrequency shown promise reversing age‐related promoting collagen synthesis, reducing age. Additionally, lifestyle diet, sleep, circadian rhythm alignment significantly influence health. Integrating dermatology represents a paradigm shift rejuvenation, allowing treatments that address visible signs underlying Using clocks provides framework tailoring individual patient needs, optimizing outcomes, extending results. Future research should focus longitudinal studies, accessibility, ethical considerations fully harness epigenetics health overall well‐being.

Язык: Английский

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