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Epi-Immunotherapy in Cancer Treatment: Mechanisms, Clinical Progress, and Future Directions.

Cancer immunotherapy is a groundbreaking therapeutic strategy, yet it continues to face significant challenges, including limited overall response rates and treatment resistance. Emerging research has demonstrated the pivotal role of epigenetic modifications in tumor immune evasion, providing a strong rationale for developing "epi-immunotherapy"-an innovative approach that combines epigenetic therapy with immunotherapy. This comprehensive review systematically examines how epigenetic regulation mediates tumor immune escape and the mechanisms involved, including suppression of tumor antigen exp

Epigenetic Mechanisms in DNA Double Strand Break Repair: A Clinical Review.

Upon the induction of DNA damage, the chromatin structure unwinds to allow access to enzymes to catalyse the repair. The regulation of the winding and unwinding of chromatin occurs via epigenetic modifications, which can alter gene expression without changing the DNA sequence. Epigenetic mechanisms such as histone acetylation and DNA methylation are known to be reversible and have been indicated to play different roles in the repair of DNA. More importantly, the inhibition of such mechanisms has been reported to play a role in the repair of double strand breaks, the most detrimental type of DN

Targeting phosphatidylinositol-3-kinase pathway for the treatment of Philadelphia-negative myeloproliferative neoplasms.

Myeloproliferative neoplasms (MPN) are a diverse group of chronic hematological disorders that involve unregulated clonal proliferation of white blood cells. Sevearl of them are associated with mutations in receptor tyrosine kinases or cytokine receptor associated tyrosine kinases rendering them independent of cytokine-mediated regulation. Classically they have been broadly divided into BCR-ABL1 fusion + ve (Ph + ve) or -ve (Ph-ve) MPNs. Identification of BCR-ABL1 tyrosine kinase as a driver of chronic myeloid leukemia (CML) and successful application of small molecule inhibitors of the tyrosi

Demethylating Agents in the Treatment of Cancer.

Gene silencing resulting from aberrant DNA methylation can lead to tumorigenesis. Therefore, drugs that inhibit or interfere with DNA methylation have been used to reactivate and induce silenced gene re-expression in malignancies. Two demethylating agents, azacitidine and decitabine, are approved for the treatment of myelodysplastic syndromes (MDS) by the U.S. Food and Drug Administration (FDA), and are now considered the standard of care in MDS. In this review, we discuss clinical data, including clinical benefits and toxicities, which led to the approval of azacitidine and decitabine. We als

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… DNA methylation landscapes: provocative insights from epigenomics. Nat. Rev. Genet. 2008;9:465–476. doi: 10.1038/nrg2341. 13. Geiman T.M., Muegge K. DNA methylation in early development. Mol. Reprod. Dev. 2010;77:105–113. doi: 10.1002/mrd.21118. 14. Guibert S., Forne T., Weber M. … Cancer epigenomics: DNA methylomes and histone-modification maps. Nat. Rev. Genet. 2007;8:286–298. doi: 10.1038/nrg2005. 33. Liu S., Ren S., Howell P., Fodstad O., Riker A.I. Identification of novel epigenetically modified genes in human melanoma via promoter methylation gene profiling. …

Advances in microsurgery and assisted reproduction for management of male infertility.

BACKGROUND: This study examines genetic diversity among 102 registered English Bulldogs used for breeding based on maternal and paternal haplotypes, allele frequencies in 33 highly polymorphic short tandem repeat (STR) loci on 25 chromosomes, STR-linked dog leukocyte antigen (DLA) class I and II haplotypes, and the number and size of genome-wide runs of homozygosity (ROH) determined from high density SNP arrays. The objective was to assess whether the breed retains enough genetic diversity to correct the genotypic and phenotypic abnormalities associated with poor health, to allow for the elimi

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… Integration with spatial epigenomic [ 182 – 189 ] and proteomic data [ 190 , 191 ] offers an opportunity to capture regulatory architecture and protein-level signaling within pathological microenvironments in the AD brain. … Integration of spatial transcriptomics with complementary modalities, including histopathological imaging data, spatial proteomics, spatial epigenomics, and genetic variation, may help connect molecular alterations to regulatory mechanisms and disease trajectories within defined brain microenvironments …

Advancements in extensive-stage small cell lung cancer therapy: from molecular profiling to the advent of precision oncology.

Small cell lung cancer (SCLC) is challenging to manage due to its high malignancy and early metastatic spread. Although initial chemoradiotherapy responses are common, resistance rapidly develops, and long-term efficacy remains limited. Immune checkpoint inhibitors (ICIs) overcome previous survival barriers, extending overall survival (OS) and progression-free survival (PFS) in extensive-stage SCLC. Nevertheless, absolute clinical benefits remain modest. To address efficacy limitations, current research focuses on optimizing first-line strategies by exploring multimodal regimens (e.g., adding

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… Moreover, whole-genome sequencing (WGS) and integrated multi-omics approaches ( 74 )—spanning genomics, transcriptomic, epigenomics, and metabolomics—are essential to elucidate mechanisms underlying SCLC pathogenesis, plasticity, metastasis, and therapy resistance. … By integrating WGS data with transcriptomic and epigenomic profiles, it is possible to reconstruct regulatory networks linking genetic alterations to functional phenotypes, thereby clarifying the molecular mechanisms underlying phenotypic transformation, metastatic progression, and drug resistance. …

A Comprehensive Review of Interventional Clinical Trials in Patients with Bone Metastases.

Bone metastasis is one of the most important factors associated with poor prognosis for patients with prostate, breast, thyroid, and lung cancer. In the past two decades, 651 clinical trials, including 554 interventional trials, were being registered in ClinicalTrials.gov and pharma.id.informa.com to combat bone metastases from different perspectives. In this review, we comprehensively analyzed, regrouped, and discussed all the interventional trials on bone metastases. Clinical trials were re-grouped into bone-targeting agents, radiotherapy, small molecule targeted therapy, combination therapy

Synthetic lethality and DNA damage response targeting in cancer stem cells: a comprehensive review.

This comprehensive review explores the critical intersection of Synthetic Lethality (SL) and DNA Damage Response (DDR) targeting within Cancer Stem Cells (CSCs), a subpopulation central to tumor initiation, metastasis, and therapeutic resistance. CSCs exhibit unique biological properties, including enhanced DNA repair mechanisms and metabolic plasticity, rendering them intrinsically resistant to conventional therapies. The fundamental mechanisms of DDR pathways and their dysregulation in cancer are delineated, highlighting how these vulnerabilities can be exploited through SL. The review synth

Application and mechanistic research of novel therapeutic strategies in cisplatin-resistant small cell lung cancer.

IntroductionSmall cell lung cancer (SCLC) initially responds well to cisplatin-based chemotherapy, but rapid development of drug resistance limits long-term efficacy and subsequent treatment options. Understanding the multifactorial mechanisms of cisplatin resistance is essential for improving patient outcomes. This review synthesizes recent preclinical and clinical advances, focusing on seven key resistance mechanisms and emerging therapeutic strategies, including immunotherapy, targeted therapy, and novel chemotherapeutic agents.DiscussionCisplatin resistance in SCLC arises through multiple

Postbiotics as Emerging Strategy Targeting Obesity- and Aging-Related Breast Cancer-Prospects in Prophylaxis and Therapy.

Aging and obesity accompanied with hormonal disequilibrium represent critical, inter-related risk factors for breast cancer, significantly influencing disease incidence, progression, and therapeutic outcomes. This review aims to elucidate the multifaceted biological mechanisms linking obesity and aging to breast carcinogenesis, with a particular focus on the emerging therapeutic and preventive potential of postbiotics as molecules targeting cellular events important for cancer growth and responsiveness. Despite continuous advancement, breast cancer therapy still poses several challenges, such

Epigenetic modification in diabetic kidney disease.

Diabetic kidney disease (DKD) is a common microangiopathy in diabetic patients and the main cause of death in diabetic patients. The main manifestations of DKD are proteinuria and decreased renal filtration capacity. The glomerular filtration rate and urinary albumin level are two of the most important hallmarks of the progression of DKD. The classical treatment of DKD is controlling blood glucose and blood pressure. However, the commonly used clinical therapeutic strategies and the existing biomarkers only partially slow the progression of DKD and roughly predict disease progression. Therefor

High-dose intravenous vitamin C, a promising multi-targeting agent in the treatment of cancer.

Mounting evidence indicates that vitamin C has the potential to be a potent anti-cancer agent when administered intravenously and in high doses (high-dose IVC). Early phase clinical trials have confirmed safety and indicated efficacy of IVC in eradicating tumour cells of various cancer types. In recent years, the multi-targeting effects of vitamin C were unravelled, demonstrating a role as cancer-specific, pro-oxidative cytotoxic agent, anti-cancer epigenetic regulator and immune modulator, reversing epithelial-to-mesenchymal transition, inhibiting hypoxia and oncogenic kinase signalling and b

Fasting boosts breast cancer therapy efficacy via glucocorticoid activation.

The majority of breast cancers are driven by oestrogen receptor-α (ERα) activation, and endocrine therapy represents the mainstay treatment for these patients1. However, resistance is common and tumours often progress after years of endocrine suppression2. Periodic fasting enhances the efficacy of standard endocrine therapy and delays acquired drug resistance, although the underlying mechanisms remain unclear3. Here we show that fasting induces extensive epigenetic reprogramming in ERα-positive breast cancer xenografts when combined with endocrine therapy, with large-scale activation of glucoc

Diffuse midline glioma treated with epigenetic agent-based immunotherapy.

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ACY‑1215, a HDAC6 inhibitor, decreases the dexamethasone‑induced suppression of osteogenesis in MC3T3‑E1 cells.

Glucocorticoid‑induced osteoporosis is the commonest form of drug‑induced osteoporosis. Histone deacetylase 6 (HDAC6) is involved in the differentiation from mesenchymal stem cells to osteoblasts. However, the role of ricolinostat (ACY‑1215, HDAC6 inhibitor) in the dexamethasone (Dex)‑induced proliferation and differentiation of preosteoblasts remains to be elucidated. The protein expression and mRNA expression levels of HDAC6, osteopontin (OPN), runt‑related transcription factor 2 (Runx2), osterix (Osx), collagen I (COL1A1) and glucocorticoid receptor (GR) in MC3T3‑E1 cells were analyzed by w

Patients Undergoing Myeloablative Chemotherapy and Hematopoietic Stem Cell Transplantation Exhibit Depleted Vitamin C Status in Association with Febrile Neutropenia.

Patients undergoing myeloablative chemotherapy and hematopoietic stem cell transplantation (HSCT) experience profound neutropenia and vulnerability to infection. Previous research has indicated that patients with infections have depleted vitamin C status. In this study, we recruited 38 patients with hematopoietic cancer who were undergoing conditioning chemotherapy and HSCT. Blood samples were collected prior to transplantation, at one week, two weeks and four weeks following transplantation. Vitamin C status and biomarkers of inflammation (C-reactive protein) and oxidative stress (protein car

Вирус Варичеллы Зостер и повторный перевод множественных склерозов.

Множественный склероз (MS) представляет собой иммунное расстройство; однако мало что известно о пусковых факторах аномальной иммунной реакции. В качестве потенциальных участников были упомянуты различные вирусы из семейства герпесов. Здесь мы анализируем доказательства, подтверждающие связь вируса варицелла-зостера (VZV) с MS. Эпидемиологические исследования, проведенные в географических районах, где в последние десятилетия наблюдалось увеличение числа случаев заболевания MS, показали высокую частотность варицелла и зостера в клинических предместьях пациентов MS, а также результаты лабораторны

Конвергенция генетики вируса хост и Эпштейн-Барр в множестве склерозов.

Недавние сероэпидемиологические исследования укрепили гипотезу о том, что вирус Эпштейн-Барр (ЭБВ) может быть причиной множественного склероза (МС). С учетом сложности взаимодействия EBV-принимателя различные механизмы могут нести ответственность за патогенез болезни. Кроме того, остается неясным, относится ли это к конкретным заболеваниям. Здесь мы показали, что гены, кодирующие взаимодействие EBV, обогащаются в лоси, связанных с MS, но не с другими заболеваниями и в приоритетных терапевтических целях. Анализ крови MS и транскриптомов мозга подтвердил дисрегулирование связанных с MS EBV интер

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… We overlapped the SNPs with the protein binding map generated by the Encyclopedia of DNA Elements (ENCODE) and RoadMap Epigenomics ( 20 ), obtaining a list of enriched proteins. … After the ALIGATOR analysis, we used the RegulomeDB database ( 20 ), that is fed with live data from ENCODE and Roadmap Epigenomics, to look for proteins binding in regions containing “postmatch” SNPs that displayed nominally significant associations with MS. …

Current perspectives on KMT2A fusion proteins and menin inhibition in paediatric acute myeloid leukaemia.

The therapeutic landscape of acute myeloid leukaemia (AML) has evolved beyond the classic '7 + 3'/DA regimen, through the approval and incorporation of targeted treatments in both front-line and relapsed/refractory settings. Indeed, the use of selective BCL-2 antagonists (e.g. venetoclax) and FLT3 inhibitors (e.g. midostaurin, gilteritinib) which target specific molecular characteristics of leukaemic cells, has enhanced outcomes and survival rates. Arguably one of the most exciting advancements has been the clinical development of menin inhibitors for the treatment of patients harbouring speci

Мультиэнштейная геномная ассоциация и мультиомикальный анализ позволяют выявить специфичные особенности многоклерозной генетики.

Множественный склероз (MS) — хроническое воспалительное заболевание центральной нервной системы, характеризующееся обезвоживанием, распространяющимся в пространстве и во времени. Здесь мы провели исследование ассоциации генома (GWAS) с использованием 688 Количество дел, связанных с НР и 205,199 :: контроль со стороны японского населения и выявление важных связей в основном сложном регионе, связанном с гистокомпьютерностью, и в 11q24 году вариант риска, учитывающий специфику населения. С помощью межнаселенных метаанализов GWAS с использованием всего 29,374 случаи и случаи 1,843,563 контроля с 4