Cold and hot tumors: from molecular mechanisms to targeted therapy

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

Опубликована: Окт. 18, 2024

Immunotherapy has made significant strides in cancer treatment, particularly through immune checkpoint blockade (ICB), which shown notable clinical benefits across various tumor types. Despite the transformative impact of ICB treatment therapy, only a minority patients exhibit positive response to it. In with solid tumors, those who respond well typically demonstrate an active profile referred as "hot" (immune-inflamed) phenotype. On other hand, non-responsive may distinct "cold" (immune-desert) phenotype, differing from features tumors. Additionally, there is more nuanced "excluded" positioned between and categories, known type. Effective differentiation understanding intrinsic factors, characteristics, TME, external factors are critical for predicting results. It widely accepted that therapy exerts profound effect on limited efficacy against or "altered" necessitating combinations therapeutic modalities enhance cell infiltration into tissue convert tumors ones. Therefore, aligning traits this review systematically delineates respective influencing extensively discusses varied approaches drug targets based assess efficacy.

Язык: Английский

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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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Uncovering the significance of CBX3 as an up-and-coming biomarker in cardio-vascular health

Epigenetics Communications, Год журнала: 2025, Номер 5(1)

Опубликована: Янв. 7, 2025

Cardiovascular disease (CVD) is the primary cause of mortality globally with a multifactorial etiology that involves epigenetics. Chromobox 3 (CBX3), major isoform heterochromatin protein 1, involved in intricate epigenetic mechanisms affecting congestive heart failure. In patients CVD affected by lung cancer risk, CBX3 exerts sophisticated mechanism action, suppressing proliferation, migration, and formation neointima vascular smooth muscle cells (VSMCs) Notch3 pathway, indicating potential protective function against remodeling atherosclerosis. However, broader im- pact on endothelial function, as well its effects monocyte/macro- phage lymphocyte infiltration within arterial wall, remain poorly understood. Since very little known so far, more definite research would be needed to reveal fine along relationship molecular processes prospects biomarker. Specifically, biological features could examined gain greater insight into risks. This review outlines role associated feasibility for optimizing pre-existing therapy developing new therapeutic strategies based personalized medicine.

Язык: Английский

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Exploring viral mimicry combined with epigenetics and tumor immunity: new perspectives in cancer therapy

International Journal of Biological Sciences, Год журнала: 2025, Номер 21(3), С. 958 - 973

Опубликована: Янв. 6, 2025

Viral mimicry refers to an active antiviral response triggered by the activation of endogenous retroviruses (ERVs), usually manifested formation double-stranded RNA (dsRNA) and cellular interferon response, which activates immune system produces anti-tumor effects. Epigenetic studies have shown that epigenetic modifications (e.g. DNA methylation, histone modifications, etc.) play a crucial role in tumorigenesis, progression, treatment resistance. Particularly, alterations methylation may be closely associated with suppression ERVs expression, demethylation restore activity thus strengthen tumor response. Therefore, we propose viral can induce responses microenvironment activating expression ERVs, key regulatory this process. In paper, review intersection mimicry, epigenetics immunotherapy, explore possible interactions synergistic effects among three, aiming provide new theoretical basis potential strategies for cancer immunotherapy.

Язык: Английский

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Nanozyme-Based Strategies in Cancer Immunotherapy: Overcoming Resistance to Enhance Therapeutic Efficacy

Aging and Disease, Год журнала: 2025, Номер unknown, С. 0 - 0

Опубликована: Янв. 1, 2025

Nanozymes, which are nanomaterials that replicate the catalytic activities of natural enzymes in biological systems, have recently demonstrated considerable potential improving cancer immunotherapy by altering tumor microenvironment. Nanozyme-driven immune responses represent an innovative therapeutic modality with high effectiveness and minimal side effects. These nanozymes activate system to specifically recognize destroy cells. Combined immunotherapeutic agents, can amplify anti-cancer integrating remodeling immunogenic cell death (ICD). This review offers a thorough discussion about various involved immunity, including those mimicking catalase (CAT), superoxide dismutase (SOD), peroxidase (POD), oxidase (OXD). It also discusses challenges future directions for translating nanozyme platforms into clinical applications, enhancing susceptibility cells immunotherapy. Nanozyme-based strategies substantial oncology, offering new effective options management.

Язык: Английский

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Secretory exosomes from modified immune cells against cancer

Medical Oncology, Год журнала: 2025, Номер 42(5)

Опубликована: Апрель 10, 2025

Язык: Английский

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Interaction between post-tumor inflammation and vascular smooth muscle cell dysfunction in sepsis-induced cardiomyopathy

Frontiers in Immunology, Год журнала: 2025, Номер 16

Опубликована: Апрель 10, 2025

Sepsis-induced cardiomyopathy (SIC) presents a critical complication in cancer patients, contributing notably to heart failure and elevated mortality rates. While its clinical relevance is well-documented, the intricate molecular mechanisms that link sepsis, tumor-driven inflammation, cardiac dysfunction remain inadequately explored. This study aims elucidate interaction between post-tumor intratumor heterogeneity, of VSMC SIC, as well evaluate therapeutic potential exercise training specific pharmacological interventions. Transcriptomic data from NCBI GEO databases were analyzed identify differentially expressed genes (DEGs) associated with SIC. Weighted gene co-expression network analysis (WGCNA), ontology (GO), KEGG pathway enrichment analyses utilized biological significance these genes. Molecular docking dynamics simulations used investigate drug-target interactions, immune infiltration mutation carried out by means platforms like TIMER 2.0 DepMap comprehend influence DVL1 on responsiveness. Through utilization datasets, we discovered core exhibited remarkable up-regulated expression both SIC diverse kinds cancers, which poor prognosis inflammatory responses. revealed Digoxin could bind reduce oxidative stress The module related was identified WGCNA, demonstrated distinctive cell patterns impact immunotherapeutic resistance. regulator other cancers and, therefore, can serve target. present suggests targeted therapies enhance response regimens may be novel tool during particularly patients. drugs, Digoxin, require further vivo studies confirm their effects efforts improve outcomes immunotherapy-resistant

Язык: Английский

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Targeting exercise-related genes and placental growth factor for therapeutic development in head and neck squamous cell carcinoma

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Окт. 4, 2024

Background Human cancers, including head and neck squamous cell carcinoma (HNSCC), are complex heterogeneous diseases driven by uncontrolled growth proliferation. Post-translational modifications (PTMs) of proteins play a crucial role in cancer progression, making them promising target for pharmacological intervention. This study aims to identify key exercise-related genes with prognostic value HNSCC through comprehensive bioinformatics analysis, particular focus on the therapeutic potential placental factor (PIGF). Methods Transcriptome data were obtained from The Cancer Genome Atlas (TCGA) database. Differently expressed (DEGs) identified analyzed their significance. Exercise-related gene sets retrieved Gene Set Enrichment Analysis (GSEA) Functional enrichment analyses, Ontology (GO), Kyoto Encyclopedia Genes Genomes (KEGG), GSEA, conducted. biological functions clinical implications further explored single-gene expression immune infiltration vitro cellular experiments. Results associated survival prognosis HNSCC. GO KEGG pathway analyses highlighted these genes, Kaplan-Meier curves confirmed value. PIGF analysis using TCGA showed its diagnostic potential, higher linked advanced tumor stages. Single-cell sequencing revealed PIGF’s microenvironment. In experiments demonstrated that plays pivotal enhancing proliferation colony formation HNSCC, knockdown significantly impairing functions, highlighting importance regulation. Additionally, predictive performance drug sensitivity across datasets suggests as target, offering opportunities modulate microenvironment improve outcomes treatment. Conclusion provides new insights into molecular mechanisms underlying identifies particularly PIGF, biomarkers treatment personalized medicine. By focusing PTMs our findings suggest targeting may offer innovative strategies.

Язык: Английский

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Optimizing CD8+ T cell-based immunotherapy via metabolic interventions: a comprehensive review of intrinsic and extrinsic modulators

Experimental Hematology and Oncology, Год журнала: 2024, Номер 13(1)

Опубликована: Окт. 22, 2024

Abstract CD8 + T cells are integral to the effective management of cancer and infectious diseases due their cytotoxic functions. The efficacy these is profoundly influenced by metabolic state, which regulates activation, differentiation, longevity. Accordingly, modulation pathways within crucial for enhancing effectiveness cell-based immunotherapy. Precise control paramount in optimizing therapeutic outcomes minimizing potential toxicities associated with treatment. Importantly, exogenous metabolites augment cell responses critically evaluated, especially through vivo evidence that underscores promise. This review also addresses current challenges, including need precise avoid adverse effects, development targeted delivery systems ensure efficient metabolite cells, inherent variability states among patients may influence treatment outcomes. Addressing hurdles will be successful integration interventions into established immunotherapeutic regimens.

Язык: Английский

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Single-cell spatial immune profiling for precision immunotherapy in Lynch syndrome

Journal of the National Cancer Center, Год журнала: 2024, Номер 5(1), С. 3 - 7

Опубликована: Дек. 7, 2024

Язык: Английский

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