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Prominent Role of Histone Modifications in the Regulation of Tumor Metastasis.

Tumor aggressiveness and progression is highly dependent on the process of metastasis, regulated by the coordinated interplay of genetic and epigenetic mechanisms. Metastasis involves several steps of epithelial to mesenchymal transition (EMT), anoikis resistance, intra- and extravasation, and new tissue colonization. EMT is considered as the most critical process allowing cancer cells to switch their epithelial characteristics and acquire mesenchymal properties. Emerging evidence demonstrates that epigenetics mechanisms, DNA methylation, histone modifications, and non-coding RNAs participate

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… However, the constant progress in the field of epigenetics, has allowed their future implementation in clinical trials and in the clinical setting as individualized therapies that specifically target each cancer’s unique “epigenome”. … Cancer epigenomics: Beyond genomics Curr. Opin. Genet. Dev. 2012 22 50 55 10.1016/j.gde.2012.02.008 22402447 44. Carmona F.J. Davalos V. Vidal E. Gomez A. Heyn H. Hashimoto Y. Vizoso M. Martinez-Cardus A. Sayols S. Ferreira H.J. …

Translation of Epigenetics in Cell-Free DNA Liquid Biopsy Technology and Precision Oncology.

Technological advancements in cell-free DNA (cfDNA) liquid biopsy have triggered exponential growth in numerous clinical applications. While cfDNA-based liquid biopsy has made significant strides in personalizing cancer treatment, the exploration and translation of epigenetics in liquid biopsy to clinical practice is still nascent. This comprehensive review seeks to provide a broad yet in-depth narrative of the present status of epigenetics in cfDNA liquid biopsy and its associated challenges. It highlights the potential of epigenetics in cfDNA liquid biopsy technologies with the hopes of enha

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… Numerous studies have shown a high frequency of mutations in genes encoding proteins that regulate epigenomic processes in cancers, and it is well established that aberrations of epigenetics machinery play a key role in tumorigenesis [ 42 , 47 , 48 ]. … Another aspect of epigenomics is identifying the apparatus and mechanisms that work together to execute epigenetic regulation. This machinery is known as epigenetic mechanisms. …

Epigenetic Mechanisms Involved in the Cardiovascular Toxicity of Anticancer Drugs.

The cardiovascular toxicity of anticancer drugs promotes the development of cardiovascular diseases. Therefore, cardiovascular toxicity is an important safety issue that must be considered when developing medications and therapeutic applications to treat cancer. Among anticancer drugs, members of the anthracycline family, such as doxorubicin, daunorubicin and mitoxantrone, are known to cause cardiotoxicity and even heart failure. Using human-induced pluripotent stem cell-derived cardiomyocytes in combination with "Omic" technologies, we identified several cardiotoxicity mechanisms and signal t

Targeted and epigenetic therapies for acute myeloid leukemia treatment.

This article provides a comprehensive overview of targeted and epigenetic therapies for acute myeloid leukemia (AML), highlighting their role in advancing treatment strategies. Recognizing that AML arises from complex genetic and epigenetic alterations, a deeper understanding of its pathogenesis has paved the way for precision medicine. The article reviews key targeted therapies, including IDH inhibitors (e.g., ivosidenib, enasidenib) for IDH mutations, FLT3 inhibitors (e.g., midostaurin, gilteritinib) for FLT3 alterations, BCL2 inhibitors (e.g., venetoclax) impacting apoptosis, and emerging M

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… Genomic and epigenomic landscapes of adult de novo acute myeloid leukemia. N Engl J Med. 2013;368(22):2059–74. 68. Dawson MA. The cancer epigenome: concepts, challenges, and therapeutic opportunities. Science. 2017;355(6330):1147–52. 69. Fathi E, et al. … A decade of exploring the cancer epigenome—biological and translational implications. Nat Rev Cancer. 2011;11(10):726–34. 153. Jones PA, Baylin SB. The epigenomics of cancer. Cell. 2007;128(4):683–92. 154. Blum W, et al. …

Deciphering and targeting oncogenic pathways through integrated approaches and amino acid metabolism in hematologic malignancies.

Hematologic malignancies, including leukemia, lymphoma, and multiple myeloma, represent a diverse group of blood cancers driven by complex oncogenic pathways and genetic aberrations. Despite advances in treatment, resistance and relapse remain significant clinical challenges. This review presents an integrative approach to blood cancer therapy, highlighting the convergence of precision medicine, CRISPR-based gene editing, immunotherapy (including CAR-T cells and immune checkpoint inhibitors), and targeted modulation of amino acid metabolism. We investigate the molecular pathways driving tumour

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… Then, multi-omics approaches simultaneously drawing on GWAS and epigenomics, metabolomics, and proteomics are expected to offer a more comprehensive understanding of blood cancer pathogenesis. … First, most GWAS-identified variants confer modest risk, and their functional consequences remain unclear without integration into functional genomics and epigenomics frameworks. …

Recent Advances on the Pathobiology and Treatment of Multiple Myeloma.

Worldwide experts in the field of multiple myeloma (MM) have promptly answered to the call in the Special Issue entitled "Recent advances on the pathobiology and treatment of multiple myeloma", submitting basic, translational or clinical works under the form of original article, review or perspective [...].

Epigenetics-targeted drugs: current paradigms and future challenges.

Epigenetics governs a chromatin state regulatory system through five key mechanisms: DNA modification, histone modification, RNA modification, chromatin remodeling, and non-coding RNA regulation. These mechanisms and their associated enzymes convey genetic information independently of DNA base sequences, playing essential roles in organismal development and homeostasis. Conversely, disruptions in epigenetic landscapes critically influence the pathogenesis of various human diseases. This understanding has laid a robust theoretical groundwork for developing drugs that target epigenetics-modifyin

Tuning epigenetics to enhance cancer virotherapy.

Cancer remains a major global health challenge, driving intensive research into novel therapeutic strategies. Oncolytic viruses (OVs) including herpesviruses, adenoviruses and echoviruses, have emerged as promising agents for cancer treatment, with several achieving regulatory approval. These viruses selectively lyse tumor cells and stimulate antitumor immunity. Nevertheless, their efficacy is constrained by limitations such as neutralization by serum factors and tumor cell resistance. Concurrently, epigenetic inhibitors modulate gene expression to suppress tumor proliferation and reshape immu

Multiple myeloma, a quintessential malignant disease of aging: a geroscience perspective on pathogenesis and treatment.

Multiple myeloma (MM) is an incurable plasma cell malignancy, which is predominantly a disease of older adults (the median age at diagnosis is 70 years). The slow progression from asymptomatic stages and the late-onset of MM suggest fundamental differences compared to many other hematopoietic system-related malignancies. The concept discussed in this review is that age-related changes at the level of terminally differentiated plasma cells act as the main risk factors for the development of MM. Epigenetic and genetic changes that characterize both MM development and normal aging are highlighted

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… Future studies should determine how age acceleration, via altering the epigenome, promotes the pathogenesis of MM. … Pawlyn C Kaiser MF Davies FE Morgan GJ Current and potential epigenetic targets in multiple myeloma Epigenomics 2014 6 2 215 228 24811790 10.2217/epi.14.12 92. …

Многомерное профилирование и модели риска, основанные на клиническом развертывании АИ, в МГУС и миеломе.

Моноклональная гаммопатия неопределённого значения (MGUS), храпающая миелома (SMM) и множественная миелома (MM) образуют континуум расстройств плазменных клеток, причем прогрессировать от MGUS до MM трудно предсказать. Нынешние модели стратификации риска, в значительной степени основанные на клинических, лабораторных и цитогенетических маркерах, не отражают молекулярную сложность, лежащую в основе развития заболеваний, что ограничивает их прогнозную точность. Последние достижения в области мультиомики, включая геномику, транскриптомику, протеомику и метаболомику, позволили глубже понять молеку

JCMM Annual Review on Advances in Biotechnology for the Treatment of Haematological Malignancies: A Review of the Latest In-Patient Developments 2024-2025.

Advances in biotechnology are set to revolutionise the treatment of haematological malignancies. Current treatments have limited efficacy due to their high toxicity and poor long-term outcomes, particularly in acute myeloid leukaemia (AML). In 2024-2025, emerging targeted therapies promise improved results with reduced adverse effects. This review is the first of an annual series exploring the latest in-patient developments in several key areas, focusing on mechanisms. We present advances in the use and action of several therapies including epigenetic modulators, protein degraders, apoptotic i

Investigating the Interplay between Myeloma Cells and Bone Marrow Stromal Cells in the Development of Drug Resistance: Dissecting the Role of Epigenetic Modifications.

Multiple Myeloma (MM) is a malignancy of plasma cells infiltrating the bone marrow (BM). Many studies have demonstrated the crucial involvement of bone marrow stromal cells in MM progression and drug resistance. Together with the BM microenvironment (BMME), epigenetics also plays a crucial role in MM development. A variety of epigenetic regulators, including histone acetyltransferases (HATs), histone methyltransferases (HMTs) and lysine demethylases (KDMs), are altered in MM, contributing to the disease progression and prognosis. In addition to histone modifications, DNA methylation also plays

Генетический риск нейродегенеративных заболеваний связан с микрогилевыми путями, учитывающими конкретные заболевания.

Исследования, проведенные в рамках общегеномной ассоциации, выявили тысячи общих вариантов, связанных с повышенным риском нейродегенеративных расстройств. Однако некодирование этих вариантов затруднило назначение целевых генов для типов мозговых клеток. Геномические подходы, которые определяют хромосомную 3D-архитектуру, могут увязать некодирующие варианты риска и дистальные элементы регулирования генов, такие, как усилители, с пропагандистами генов. Используя карты улучшения взаимодействия для микроглии, нейронов и олигодендроцитов, мы определили конкретное обогащение генетической наследствен

Polyphenols bind G4-Quadruplex structures and act as epigenetic modifiers with anti-cancer effects.

G4-quadruplexes (G4s) are non-canonical structures of nucleic acids that develop in guanine rich regions of DNA and RNA. Due to their presence in oncogenic promoters and telomeres, G4s represent attractive targets in anticancer drug designs. G4s have also been the subject of recent research regarding their role as epigenetic modulators, supporting their participation in epigenetic processes that control gene expression. The development of small compounds that preferentially target G4s have led to a better understanding of how G4s control these mechanisms. Natural products have greatly contribu

The epigenetic revolution in hematology: from benchside breakthroughs to clinical transformations.

The field of hematology has experienced a substantial evolution with the acknowledgment of epigenetic processes as essential factors in the development of hematological malignancies. This review article examines the influence of epigenetic alterations, namely DNA methylation and histone modifications, on the onset and advancement of conditions such as acute myeloid leukemia and myelodysplastic syndromes. We discuss how these epigenetic modifications lead to the deregulation of gene expression, eventually promoting leukemogenesis. The emergence of epigenetic therapies, such as DNA methyltransfe

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… Other technologies related to epigenetics and genetics include single-cell epigenomics, which has been used in hematopoietic processes and the study of leukemic cells. … CRISPR technologies for precise epigenome editing. Nat Cell Biol. 2021;23(1):11–22. 141. Hilton IB, et al. Epigenome editing by a CRISPR-Cas9-based acetyltransferase activates genes from promoters and enhancers. Nat Biotechnol. 2015;33(5):510–7. 142. Bester AC, et al. …

Transforming tumor microenvironments: nanotechnology and gene therapy in cellular signaling and epigenetic insight into chemo-resistance.

Chemoresistance remains the primary cause of cancer treatment failure, yet current understanding remains fragmented across isolated mechanistic studies. This review provides a unified framework linking tumor microenvironment (TME) signaling, epigenetic reprogramming, and nanotherapeutic intervention as an integrated axis driving and potentially reversing chemoresistance. We systematically examine how TME components: hypoxia (HIF-1α pathway), acidosis, cancer-associated fibroblasts (TGF-β/PDGF signaling), and immune cells (NF-κB-mediated immunosuppression) activate signaling cascades that direc

Role of microRNAs in hematological malignancies research: A bibliometric analysis.

ObjectivesMicroRNAs (miRNAs) are pivotal regulators of cancer biology, including hematological malignancies. Their roles include tumor suppression, oncogenic activities, modulation of immune responses, and treatment resistance. This study aimed to provide a quantitative analysis of research trends, thematic evolution, and key contributions to the field of miRNAs and hematological malignancies.MethodsUsing BIBLIO-Checklist and advanced visualization tools (VOSviewer and bibliometrix), data from key databases were analyzed for publication trends, author co-citations, thematic clusters, and emerg

5-Hydroxymethylcytosine modifications in circulating cell-free DNA: frontiers of cancer detection, monitoring, and prognostic evaluation.

Developing accurate, clinically convenient, and non-invasive methods for early cancer detection, monitoring, and prognosis assessment is essential for improving patient survival rates, enhancing quality of life, and reducing the socioeconomic burden associated with cancer. This goal is critical in precision oncology. Genetic and epigenetic alterations in circulating cell-free DNA (cfDNA) have emerged as transformative tools for advancing early cancer detection, monitoring, and improving patient outcomes. Among these, 5-hydroxymethylcytosine (5hmC) modifications in circulating cfDNA stand out a

Genomic innovations in cancer prevention, diagnosis, prognosis and precision therapeutics.

Cancer research has undergone a transformative change with the advent of high-throughput genomic technologies. Advances in next-generation sequencing accelerated the identification of somatic and germline alterations that drive tumorigenesis enabling the transition from traditional histology-based cancer classification to molecularly informed precision oncology. Large-scale sequencing initiatives and clinical genomic profiling facilitated the development of companion diagnostic assays and targeted therapies. Beyond targeted therapies, genomic innovations have also catalyzed the emergence of no

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… Efforts to simultaneously profile RNA, epigenome, and protein at single-cell resolution are advancing. … FIGURE 5 Epigenomic landscape in cancer. Role of epigenomics in cancer diagnosis, prognosis and precision therapeutics that resulted in key milestones achievement in cancer research and translational medicine. …

New genomic and proteomic biomarker discovery in cancer: revolutionizing diagnosis and prognostication.

Cancer remains a major global health challenge, with substantial morbidity and mortality worldwide. Advances in genomic and proteomic biomarker discovery have transformed cancer diagnosis, prognosis, and treatment selection. The evolution from early serological markers such as carcinoembryonic antigen (CEA) and prostate-specific antigen (PSA) to modern multi-omics approaches enabled by next-generation sequencing (NGS), mass spectrometry (MS), and advanced bioinformatics has revolutionized personalized medicine and targeted therapy, leading to improved outcomes. This review highlights the histo

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… While genomic biomarkers remain foundational in oncology, their ability to predict outcomes is increasingly being enhanced or complemented by transcriptomic, proteomic, and epigenomic signatures. … Multi-omics technologies, including genomics, transcriptomics, proteomics, metabolomics, and epigenomics, have significantly accelerated biomarker discovery; however, their integration into routine clinical oncology still lags far behind their rapidly growing presence in research. …