Metastasis

Cell, Год журнала: 2023, Номер 186(8), С. 1564 - 1579

Опубликована: Апрель 1, 2023

Язык: Английский

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Aging and cancer

Molecular Cancer, Год журнала: 2024, Номер 23(1)

Опубликована: Май 18, 2024

Abstract Aging and cancer exhibit apparent links that we will examine in this review. The null hypothesis aging coincide because both are driven by time, irrespective of the precise causes, can be confronted with idea share common mechanistic grounds referred to as ‘hallmarks’. Indeed, several hallmarks also contribute carcinogenesis tumor progression, but some molecular cellular characteristics may reduce probability developing lethal cancer, perhaps explaining why very old age (> 90 years) is accompanied a reduced incidence neoplastic diseases. We discuss possibility process itself causes meaning time-dependent degradation supracellular functions accompanies produces byproduct or ‘age-associated disease’. Conversely, its treatment erode health drive process, has dramatically been documented for survivors diagnosed during childhood, adolescence, young adulthood. conclude connected superior including endogenous lifestyle factors, well bidirectional crosstalk, together render not only risk factor an important parameter must considered therapeutic decisions.

Язык: Английский

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DNA methylation in mammalian development and disease

Nature Reviews Genetics, Год журнала: 2024, Номер unknown

Опубликована: Авг. 12, 2024

The DNA methylation field has matured from a phase of discovery and genomic characterization to one seeking deeper functional understanding how this modification contributes development, ageing disease. In particular, the past decade seen many exciting mechanistic discoveries that have substantially expanded our appreciation for generic, evolutionarily ancient can be incorporated into robust epigenetic codes. Here, we summarize current distinct landscapes emerge over mammalian lifespan discuss they interact with other regulatory layers support diverse functions. We then review rising interest in alternative patterns found during senescence somatic transition cancer. Alongside advancements single-cell long-read sequencing technologies, collective insights made across these fields offer new opportunities connect biochemical genetic features cell physiology, developmental potential phenotype. Review, Smith et al. describe development within key disease states, as well different methyltransferases interface histone modifications proteins create maintain them.

Язык: Английский

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Magnesium and the Hallmarks of Aging

Nutrients, Год журнала: 2024, Номер 16(4), С. 496 - 496

Опубликована: Фев. 9, 2024

Magnesium is an essential ion in the human body that regulates numerous physiological and pathological processes. deficiency very common old age. Age-related chronic diseases aging process itself are frequently associated with low-grade inflammation, called ‘inflammaging’. Because magnesium insufficiency has been linked to excessive generation of inflammatory markers free radicals, inducing a state, we formerly hypothesized inadequacy may be considered among intermediaries helping us explain link between inflammaging aging-associated diseases. We show this review evidence relationship all hallmarks (genomic instability, telomere attrition, epigenetic alterations, loss proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, altered intercellular communication, disabled autophagy, dysbiosis, inflammation), which positively affect healthspan. It feasible hypothesize maintaining optimal balance during one’s life course turn out safe economical strategy contributing promotion healthy aging. Future well-designed studies necessary further explore hypothesis.

Язык: Английский

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Epigenetic regulation in cancer therapy: From mechanisms to clinical advances

MedComm – Oncology, Год журнала: 2024, Номер 3(1)

Опубликована: Янв. 4, 2024

Abstract Epigenetic regulation refers to the alteration of gene expression independent changes in DNA sequence. It involves chemical modifications such as methylation, histone and acetylation, which are regulated by a coordinated interplay various regulators ensure precise spatial temporal expression. aberrations commonly observed cancer considered hallmarks cancer. In recent years, small molecules targeting specific epigenetic have been developed demonstrating promising therapeutic potential preclinical clinical trials for treatment. this review, we summarize essential regulatory mechanisms dysfunctions involved acetylation during tumor development progression. Moreover, discuss current advances challenges therapy that target these both hematologic malignancies solid tumors. Finally, combining drugs with other therapies, including chemotherapy, radiotherapy, targeted therapy, immunotherapy, approach Overall, aim enhance understanding explore strategies based on mechanisms, ultimately advance improve patient prognosis.

Язык: Английский

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The Epigenetic Hallmarks of Cancer

Cancer Discovery, Год журнала: 2024, Номер 14(10), С. 1783 - 1809

Опубликована: Окт. 4, 2024

Abstract Cancer is a complex disease in which several molecular and cellular pathways converge to foster the tumoral phenotype. Notably, latest iteration of cancer hallmarks, “nonmutational epigenetic reprogramming” was newly added. However, epigenetics, much like genetics, broad scientific area that deserves further attention due its multiple roles initiation, progression, adaptive nature. Herein, we present detailed examination hallmarks affected human cancer, elucidating genes involved, dissecting disrupted landscapes for DNA methylation, histone modifications, chromatin architecture define disease. Significance: characterized by constant evolution, spanning from initial premalignant stages advanced invasive disseminated stages. It pathology able adapt survive amidst hostile microenvironments diverse treatments implemented medical professionals. The more fixed setup genetic structure cannot fully provide transformed cells with tools but rapid plastic nature changes ready task. This review summarizes ecological success our bodies.

Язык: Английский

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Epigenetic regulation in cancer

MedComm, Год журнала: 2024, Номер 5(2)

Опубликована: Фев. 1, 2024

Abstract Epigenetic modifications are defined as heritable changes in gene activity that do not involve the underlying DNA sequence. The oncogenic process is driven by accumulation of alterations impact genome's structure and function. Genetic mutations, which directly disrupt sequence, complemented epigenetic modulate expression, thereby facilitating acquisition malignant characteristics. Principals among these shifts methylation histone mark patterns, promote tumor development metastasis. Notably, reversible nature alterations, opposed to permanence genetic changes, positions machinery a prime target discovery novel therapeutics. Our review delves into complexities regulation, exploring its profound effects on initiation, metastatic behavior, metabolic pathways, microenvironment. We place particular emphasis dysregulation at each level modulation, including but limited to, aberrations enzymes responsible for modification, subunit loss or fusions chromatin remodeling complexes, disturbances higher‐order structure. Finally, we also evaluate therapeutic approaches leverage growing understanding dysregulation, offering new avenues cancer treatment.

Язык: Английский

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Role of LMO7 in cancer (Review)

Oncology Reports, Год журнала: 2024, Номер 52(3)

Опубликована: Июль 11, 2024

Язык: Английский

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Redox regulation: mechanisms, biology and therapeutic targets in diseases

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Март 7, 2025

Redox signaling acts as a critical mediator in the dynamic interactions between organisms and their external environment, profoundly influencing both onset progression of various diseases. Under physiological conditions, oxidative free radicals generated by mitochondrial respiratory chain, endoplasmic reticulum, NADPH oxidases can be effectively neutralized NRF2-mediated antioxidant responses. These responses elevate synthesis superoxide dismutase (SOD), catalase, well key molecules like nicotinamide adenine dinucleotide phosphate (NADPH) glutathione (GSH), thereby maintaining cellular redox homeostasis. Disruption this finely tuned equilibrium is closely linked to pathogenesis wide range Recent advances have broadened our understanding molecular mechanisms underpinning dysregulation, highlighting pivotal roles genomic instability, epigenetic modifications, protein degradation, metabolic reprogramming. findings provide foundation for exploring regulation mechanistic basis improving therapeutic strategies. While antioxidant-based therapies shown early promise conditions where stress plays primary pathological role, efficacy diseases characterized complex, multifactorial etiologies remains controversial. A deeper, context-specific signaling, particularly redox-sensitive proteins, designing targeted aimed at re-establishing balance. Emerging small molecule inhibitors that target specific cysteine residues proteins demonstrated promising preclinical outcomes, setting stage forthcoming clinical trials. In review, we summarize current intricate relationship disease also discuss how these insights leveraged optimize strategies practice.

Язык: Английский

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Virtual screening and molecular dynamics simulations identify repurposed drugs as potent inhibitors of Histone deacetylase 1: Implication in cancer therapeutics

PLoS ONE, Год журнала: 2025, Номер 20(1), С. e0316343 - e0316343

Опубликована: Янв. 3, 2025

Epigenetic processes are the critical events in carcinogenesis. Histone modification plays a crucial role gene expression regulation, where histone deacetylases (HDACs) key players epigenetic processes. Inhibiting HDACs has shown promise modern cancer therapy. However, non-selective nature and drug resistance of most HDAC inhibitors (HDACIs) limits their clinical use. This limitation prompts search for isoform-selective more effective inhibitors. deacetylase 1 (HDAC1) is member class I family emerged as promising target various diseases, including neurodegeneration. Drug repurposing gained significant interest identifying treatments new targets, which involves finding uses existing drugs beyond original medical indications. Here, we employed virtual screening repurposed from DrugBank database to identify potential HDAC1 We conducted series analyses, molecular docking, profiling, PASS evaluation, interaction analysis. Molecular dynamics (MD) simulations MM-PBSA analysis were also performed 300 ns. Through these pinpointed Alectinib, exhibits profile higher affinity efficiency than reference inhibitor. MD revealed that Alectinib stabilizes with minimal structural perturbations. The findings suggest holds therapeutic lead HDAC1-associated carcinogenesis after required validation.

Язык: Английский

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