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Epithelial-Mesenchymal Transition in Cancer: Insights Into Therapeutic Targets and Clinical Implications.

Radiation therapy is a fundamental component of cancer treatment, benefiting 50%-70% of patients by selectively targeting malignant tissues. However, radioresistance remains a significant challenge, often driven by epithelial-mesenchymal transition (EMT). EMT increases cancer invasiveness and metastasis by upregulating mesenchymal markers, including vimentin and N-cadherin, and downregulating epithelial markers, such as E-cadherin. EMT under radiation involves principal signaling pathways, including TGF-β, Wnt/β-catenin, Notch, and ERK, which regulate EMT through transcription factors such as

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… Integrated approaches, including transcriptomics, proteomics, and epigenomics, can help identify responsive patient populations and novel therapeutic targets. … Because EMT occurs across a spectrum, including epithelial, mesenchymal, and hybrid stages, multi‐omics profiling, including transcriptomics, proteomics, and epigenomics, is critical. …

From Bench to Bedside and Beyond: Therapeutic Scenario in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous group of clonal disorders characterized by abnormal proliferation of undifferentiated myeloid progenitors, impaired hematopoiesis, and variable response to therapy. To date, only about 30% of adult patients with AML become long-term survivors and relapse and/or disease refractoriness are the major cause of treatment failure. Thus, this is an urgent unmet clinical need and new drugs are envisaged in order to ameliorate disease survival outcomes. Here, we review the latest therapeutic approaches (investigational and approved agents) for AML treatme

Пространственные омики нейроинфламмации: осмысления заболеваний мозга.

Нейроинфламмация является общей патологической особенностью различных заболеваний мозга, однако подстрекательская активность редко распределяется равномерно по заболевшим тканям. Вместо этого микроглии, астроциты, проникающие в иммунные клетки и подстрекательские посредники, часто организуются вокруг конкретных патологических структур, включая амилоидные таблетки, демиелинированные поражающие ободья, ишемические границы, некротические области опухоли и белые отсеки периваскулярной материи. Хотя в рамках одноклеточных подходов, основанных на оптовых и диссоциационных подходах, было определено м

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… The technology search block included “spatial transcriptomics,” “spatial multi-omics,” “spatial proteomics,” “spatial metabolomics,” “spatial epigenomics,” “spatial ATAC-seq,” “spatial CUT&Tag,” “mass spectrometry imaging,” “MALDI imaging,” “DESI imaging,” “ in situ sequencing,” “imaging mass cytometry … Spatial-CUT&Tag and spatial-ATAC-seq are spatial epigenomic methods and, when used alone, should not be classified as multi-omic assays, although they can provide an epigenomic component within a multimodal experimental design ( 30 , 31 ). …

PSMA4 as a Druggable Target in Hidradenitis Suppurativa: Evidence From Mendelian Randomization and Single-Cell Transcriptomics.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendelian randomization (MR) analysis using blood cis-expression quantitative trait locus (eQTL) and HS genome-wide association study (GWAS) data. Colocalization, transcriptomic validation, single-cell RNA sequencing, and cell-cell communication analyses were integrated to explore gene function and cell-type specificity. We identified eight genes that showed significant associations

Predicting new drug indications for prostate cancer: The integration of an in silico proteochemometric network pharmacology platform with patient-derived primary prostate cells.

BackgroundDrug repurposing enables the discovery of potential cancer treatments using publically available data from over 4000 published Food and Drug Administration approved and experimental drugs. However, the ability to effectively evaluate the drug's efficacy remains a challenge. Impediments to broad applicability include inaccuracies in many of the computational drug-target algorithms and a lack of clinically relevant biologic modeling systems to validate the computational data for subsequent translation.MethodsWe have integrated our computational proteochemometric systems network pharmac

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… Expression analysis was performed in the Georgetown‐Lombardi Genomics and Epigenomics Shared Resource using the HumanHT ‐ 12 v4 Expression BeadChip. … ACKNOWLEDGMENTS The following Georgetown‐Lombardi Comprehensive Cancer Center core facilities were used throughout the study: the Genomics and Epigenomics Shared Resource, the Histology and Tissue Shared Resource, the Cell Culture Shared Resource and the Computational Chemistry Shared Resource The study …

Targeting the Sonic Hedgehog-Gli1 Pathway as a Potential New Therapeutic Strategy for Myelodysplastic Syndromes.

The complex mechanistic array underlying the pathogenesis of myelodysplastic syndrome (MDS) is still unclear. Although dysregulations of different signaling pathways involved in MDS have been described, the identification of specific biomarkers and therapy targets remains an important task in order to establish novel therapeutic approaches. Here, we demonstrated that the Shh signaling pathway is active in MDS and correlated it with disease progression. Additionally, the knockdown of Gli1 significantly inhibited cell proliferation in vitro and in vivo. Gli1 silencing also induced apoptosis and

Non-invasive characterization of human bone marrow stimulation and reconstitution by cell-free messenger RNA sequencing.

Circulating cell-free mRNA (cf-mRNA) holds great promise as a non-invasive diagnostic biomarker. However, cf-mRNA composition and its potential clinical applications remain largely unexplored. Here we show, using Next Generation Sequencing-based profiling, that cf-mRNA is enriched in transcripts derived from the bone marrow compared to circulating cells. Further, longitudinal studies involving bone marrow ablation followed by hematopoietic stem cell transplantation in multiple myeloma and acute myeloid leukemia patients indicate that cf-mRNA levels reflect the transcriptional activity of bone

Machine learning in onco-pharmacogenomics: a path to precision medicine with many challenges.

Over the past two decades, Next-Generation Sequencing (NGS) has revolutionized the approach to cancer research. Applications of NGS include the identification of tumor specific alterations that can influence tumor pathobiology and also impact diagnosis, prognosis and therapeutic options. Pharmacogenomics (PGx) studies the role of inheritance of individual genetic patterns in drug response and has taken advantage of NGS technology as it provides access to high-throughput data that can, however, be difficult to manage. Machine learning (ML) has recently been used in the life sciences to discover

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… Again, the best choice between the two strategies must be balanced between cost and application. 2.3 Epigenomics Epigenomic sequencing has proliferated in recent years. Epigenetics is a branch of biology that studies the causal interactions between genes and their products. … Epigenomics and transcriptomics/proteomics data can be aligned to explain how epigenetic changes can affect protein turnover ( Wang X et al., 2021 ). …

Неудовлетворение влияния полиморфизма HHEX rs7923837 на патогенез с множественным склерозом.

One (MS) риск полиморфизма, rs7923837, карты вблизи гена HHEX (гематопоэтический гомеобокс). Этот вариант также связан с типом 2 Уязвимость диабета и уровень триглицерида, что говорит о его участии в метаболике. HHEX играет важную роль в качестве негативного регулятора воспалительных генов в микроглии. Сообщалось о взаимных репрессиях между HHEX и BCL6, еще один предполагаемый фактор риска в РС. Настоящее исследование свидетельствует о статистически значимых более низких уровнях содержания HHEX mRNA в лимфоцитах пациентов с НР по сравнению с уровнем контроля, что свидетельствует о аналогичной

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… Cell type-specific transcriptomic and epigenomic maps aid in the interpretation of the potential regulatory impact of rs7923837. … The information provided by the Roadmap Epigenomics Project (roadmapepigenomics.org, accessed on 17 May 2022) revealed that this variant maps in a region that presents low transcriptional activity in PBMCs, as shown by high levels of repressive H3K27me3 histone methylation and low levels of H3K36me3 …

Targeting epigenetic methylation: emerging diagnosis and therapeutic strategies in cancer.

Epigenetics shapes all aspects of cancer occurrence and progression. Among them, chromatin methylation is a particularly important regulator of oncogenic processes. The dynamic shifts in methylation can influence the development or death of tumor cells. In the therapeutic context, effectively targeting and modulating DNA, RNA, and histone methylation brings promise for the early detection, prognostic assessment, and treatment of cancer. In particular, novel methylation inhibitors or modulators powerfully kill tumor cells or improve existing therapeutic strategies through different signaling pa

Prognostic heterogeneity and clonal dynamics within distinct subgroups of myelodysplastic syndrome and acute myeloid leukemia with TP53 disruptions.

TP53 aberrations constitute the highest risk subset of myelodysplastic neoplasms (MDS) and acute myeloid leukemia (AML). The International Consensus Classification questions the blast threshold between MDS and AML. In this study, we assess the distinction between MDS and AML for 76 patients with TP53 aberrations. We observed no significant differences between MDS and AML regarding TP53 genomics. Median overall survival (OS) was 223 days for the entire group, but prognostic discrimination within subgroups showed the most inferior OS (46 days) for AML with multihit allelic state plus TP53 varian

Mechanisms and Clinical Applications of Genome Instability in Multiple Myeloma.

Ongoing genomic instability represents a hallmark of multiple myeloma (MM) cells, which manifests largely as whole chromosome- or translocation-based aneuploidy. Importantly, although it supports tumorigenesis, progression and, response to treatment in MM patients, it remains one of the least understood components of malignant transformation in terms of molecular basis. Therefore these aspects make the comprehension of genomic instability a pioneering strategy for novel therapeutic and clinical speculations to use in the management of MM patients. Here we will review mechanisms mediating genom

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… The epigenomics of cancer Cell 2007 128 4 683 692 10.1016/j.cell.2007.01.029 2-s2.0-33847065486 17320506 PMC3894624 53 Morgan G. J. Johnson D. C. Weinhold N. … Histone methyltransferase MMSET/NSD2 alters EZH2 binding and reprograms the myeloma epigenome through global and focal changes in H3K36 and H3K27 methylation PLoS Genetics 2014 10 9 e1004566 10.1371/journal.pgen.1004566 2-s2.0-84907572364 PMC4154646 25188243 68 Jefford C. E. Irminger-Finger I. …

Machine Learning for Multi-Omics Characterization of Blood Cancers: A Systematic Review.

Artificial Intelligence and machine learning are increasingly used to interrogate complex biological data. This systematic review evaluates their application to multi-omics for the molecular characterization of hematological malignancies, an area with unmet clinical need. We searched PubMed, Embase, Institute of Electrical and Electronics Engineers Xplore, and Web of Science from January 2015 to December 2024. Two reviewers screened records, extracted data, and used a modified appraisal emphasizing explainability, performance, reproducibility, and ethics. From 2847 records, 89 studies met incl

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… Multi-omics technologies—such as genomics, transcriptomics, proteomics, metabolomics, and epigenomics—have shed light on the molecular heterogeneity underlying these diseases, revealing distinct molecular subtypes with unique therapeutic vulnerabilities, resistances, and prognostic implications. … Inclusion Criteria Studies applying AI/ML methods to the molecular characterization of hematological malignancies; Use of omics data (genomics, transcriptomics, proteomics, metabolomics, epigenomics); Peer-reviewed articles published between 1 January 2015 and 31 December 2024; Studies reporting …

Biological Age, Aging Clocks, and the Interplay with Lymphoid Neoplasms: Mechanisms and Clinical Frontiers.

Lymphoid neoplasms (LN), a diverse group of malignancies arising from lymphocytes, exhibit a striking increase in incidence with chronological age, suggesting a deep connection with the aging process. While chronological age remains a primary risk factor, the concept of biological age, reflecting an individual's physiological state and susceptibility to age-related diseases, offers a more nuanced understanding of this relationship. Aging clocks, particularly epigenetic clocks based on DNA methylation, provide quantitative measures of biological age and have revealed associations between accele

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… Furthermore, “omics”-based predictors derived from transcriptomics, proteomics, metabolomics, and notably, epigenomics, offer high-dimensional data for estimating biological age [ 54 , 58 ]. … Recent advances in causal inference for epigenetic aging, including epigenome-wide Mendelian randomization approaches, provide tools to identify causal methylation sites [ 9 , 13 ]. …

DHCR24 in Tumor Diagnosis and Treatment: A Comprehensive Review.

As an important nutrient in the human body, cholesterol can not only provide structural components for the body's cells, but also can be transformed into a variety of active substances to regulate cell signaling pathways. As an important cholesterol synthase, DHCR24 participates in important regulatory processes in the body. The application of DHCR24 in tumor clinical diagnosis and treatment also attracts much attention. This article reviews the structure and regulatory characteristics of DHCR24, and the research of DHCR24 on tumor progression. We summarize the possible mechanisms of DHCR24 pr

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… Epigenomics. 2021;13(12):919-925. doi: 10.2217/epi-2020-0442 72. Braun KVE, Dhana K, de Vries PS, et al. Epigenome-wide association study (EWAS) on lipids: The rotterdam study. Clin Epigenetics. 2017;9:15. doi: 10.1186/s13148-016-0304-4 73. Dhana K, Braun KVE, Nano J, et al. … An epigenome-wide association study of obesity-related traits. Am J Epidemiol. 2018;187(8):1662-1669. doi: 10.1093/aje 74. Zaghlool SB, Mook-Kanamori DO, Kader S, et al. Deep molecular phenotypes link complex disorders and physiological insult to CpG methylation. …

Emerging Role of Epigenetic Modifiers in Breast Cancer Pathogenesis and Therapeutic Response.

Breast cancer pathogenesis, treatment, and patient outcomes are shaped by tumor-intrinsic genomic alterations that divide breast tumors into molecular subtypes. These molecular subtypes often dictate viable therapeutic interventions and, ultimately, patient outcomes. However, heterogeneity in therapeutic response may be a result of underlying epigenetic features that may further stratify breast cancer patient outcomes. In this review, we examine non-genetic mechanisms that drive functional changes to chromatin in breast cancer to contribute to cell and tumor fitness and highlight how epigeneti

Drugs and Epigenetic Molecular Functions. A Pharmacological Data Scientometric Analysis.

Interactions of drugs with the classical epigenetic mechanism of DNA methylation or histone modification are increasingly being elucidated mechanistically and used to develop novel classes of epigenetic therapeutics. A data science approach is used to synthesize current knowledge on the pharmacological implications of epigenetic regulation of gene expression. Computer-aided knowledge discovery for epigenetic implications of current approved or investigational drugs was performed by querying information from multiple publicly available gold-standard sources to (i) identify enzymes involved in c

Gene editing and CRISPR in the clinic: current and future perspectives.

Genome editing technologies, particularly those based on zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPR (clustered regularly interspaced short palindromic repeat DNA sequences)/Cas9 are rapidly progressing into clinical trials. Most clinical use of CRISPR to date has focused on ex vivo gene editing of cells followed by their re-introduction back into the patient. The ex vivo editing approach is highly effective for many disease states, including cancers and sickle cell disease, but ideally genome editing would also be applied to diseases whic

Epigenetic and Transcriptomic Regulation Landscape in HPV+ Cancers: Biological and Clinical Implications.

Human Papillomavirus (HPV) is an oncogenic virus that causes the highest number of viral-associated cancer cases and deaths worldwide, with more than 690,000 new cases per year and 342,000 deaths only for cervical cancer (CC). Although the incidence and mortality rates for CC are declining in countries where screening and vaccination programs have been implemented, other types of cancer in which HPV is involved, such as oropharyngeal cancer, are increasing, particularly in men. Mutational and transcriptional profiles of various HPV-associated neoplasms have been described, and accumulated evid

Воздействие окисляющего стресса Gene Protein, экспрессии и метилирования ДНК на множественный склероз: многомерное исследование менделий.

СПРАВОЧНАЯ ИНФОРМАЦИЯ: Окисляющий стресс (ОС) связан с развитием множественного склероза (MS), однако причинно-следственная связь с точки зрения генетической патофизиологии остается неясной. Мы использовали менделианскую случайность (MR) и анализ совместной локализации для изучения взаимосвязи между генами ОС и MS с использованием комплексного подхода, основанного на мультиомике. МЕТОДЫ: Мы получили данные по результатам исследования, проведенного в рамках всей ассоциации по геному (GWAS) MS, из Международного консорциума по многоразовым склерозовым генетикам (этап обнаружения) и исследования

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… Integrate single‐cell transcriptomics and epigenomics to explore regulatory networks in MS. Validate the role of STAT3 in MS using animal models (e.g., EAE) and patient‐derived samples. Optimize and test drug candidates, such as quercetin, in preclinical and clinical trials. … Integrate single‐cell transcriptomics and epigenomics to explore regulatory networks in MS. …