NF-κB in biology and targeted therapy: new insights and translational implications

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

Опубликована: Март 4, 2024

Abstract NF-κB signaling has been discovered for nearly 40 years. Initially, was identified as a pivotal pathway in mediating inflammatory responses. However, with extensive and in-depth investigations, researchers have that its role can be expanded to variety of mechanisms, biological processes, human diseases, treatment options. In this review, we first scrutinize the research process signaling, summarize composition, activation, regulatory mechanism signaling. We investigate interaction other important pathways, including PI3K/AKT, MAPK, JAK-STAT, TGF-β, Wnt, Notch, Hedgehog, TLR The physiological pathological states well intricate involvement inflammation, immune regulation, tumor microenvironment, are also explicated. Additionally, illustrate how is involved cancers, autoimmune cardiovascular metabolic neurological COVID-19. Further, discuss therapeutic approaches targeting IKK inhibitors, monoclonal antibodies, proteasome nuclear translocation DNA binding TKIs, non-coding RNAs, immunotherapy, CAR-T. Finally, provide an outlook field hope present stereoscopic, comprehensive will inform future clinical practice.

Язык: Английский

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Post-Translational Modifications of Proteins Orchestrate All Hallmarks of Cancer

Life, Год журнала: 2025, Номер 15(1), С. 126 - 126

Опубликована: Янв. 18, 2025

Post-translational modifications (PTMs) of proteins dynamically build the buffering and adapting interface between oncogenic mutations environmental stressors, on one hand, cancer cell structure, functioning, behavior. Aberrant PTMs can be considered as enabling characteristics long they orchestrate all malignant variability in proteome cells, cancer-associated tumor microenvironment (TME). On other enhance anticancer mechanisms tumoral ecosystem or sustain beneficial effects oncologic therapies through degradation inactivation carcinogenic or/and activation tumor-suppressor proteins. In this review, we summarized analyzed a wide spectrum involved regulatory that drive tumorigenesis, genetic instability, epigenetic reprogramming, events metastatic cascade, cytoskeleton extracellular matrix (ECM) remodeling, angiogenesis, immune response, tumor-associated microbiome, metabolism rewiring most important hallmarks cancer. All develop due to proteins, which modulate gene transcription, intracellular signaling, protein size, activity, stability localization, trafficking, secretion, half-life, protein–protein interactions (PPIs). associated with exploited better understand underlying molecular heterogeneous chameleonic disease, find new biomarkers progression prognosis, personalize oncotherapies, discover targets for drug development.

Язык: Английский

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Flavonoids as promising molecules in the cancer therapy: An insight

Current Research in Pharmacology and Drug Discovery, Год журнала: 2023, Номер 6, С. 100167 - 100167

Опубликована: Дек. 8, 2023

Cancer continues to increase global morbidity and mortality rates. Despite substantial progress in the development of various chemically synthesized anti-cancer drugs, poor prognosis disease still remains a big challenge. The most common drawback conventional cancer therapies is emergence drug resistance eventually leading discontinuation chemotherapy. Moreover, advanced target-specific including immunotherapy stem cell therapy are expensive enough unaffordable for patients poorer nations. Therefore, alternative cheaper therapeutic strategies needed complement current treatment approaches. Phytochemicals bioactive compounds produced naturally by plants have great potential human health disease. These possess antiproliferative, anti-oxidant, immunomodulatory properties. Among phytochemicals, flavonoids very effective treating wide range diseases from cardiovascular immunological disorders cancer. They scavenge reactive oxygen species (ROS), inhibit metastasis, modulate immune system induce apoptotic or autophagic death cancers. This review will discuss phytochemicals particularly attempts target

Язык: Английский

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Low-grade Chronic Inflammation: A Shared Mechanism for Chronic Diseases

Physiology, Год журнала: 2024, Номер 40(1), С. 000 - 000

Опубликована: Июль 30, 2024

Inflammation is an important physiological response of the organism to restore homeostasis upon pathogenic or damaging stimuli. However, persistence harmful trigger a deficient resolution process can evolve into state low-grade, chronic inflammation. This condition strongly associated with development several increasingly prevalent and serious conditions, such as obesity, cancer, cardiovascular diseases, elevating overall morbidity mortality worldwide. The current pandemic diseases underscores need address inflammation, its mechanisms, potential preventive measures limit widespread impact. present review discusses knowledge research gaps regarding association between low-grade inflammation focusing on digestive cancer. We examine art in selected aspects topic propose future directions approaches for field.

Язык: Английский

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Stimulation, regulation, and inflammaging interventions of natural compounds on nuclear factor kappa B (NF-kB) pathway: a comprehensive review

Inflammopharmacology, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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Bisphenol A and DDT disrupt adipocyte function in the mammary gland: implications for breast cancer risk and progression

Frontiers in Oncology, Год журнала: 2025, Номер 15

Опубликована: Фев. 17, 2025

As breast cancer incidence continues to rise worldwide, there is a pressing need understand the environmental factors that contribute its development. Obesogens, including Bisphenol A (BPA) and Dichlorodiphenyltrichloroethane (DDT), are highly prevalent in environment, have been associated with obesity metabolic dysregulation. BPA DDT, known disrupt hormone signaling epithelial cells, also promote adipogenesis, lipogenesis, adipokine secretion adipose tissue, directly contributing pathogenesis of obesity. While adipose-rich mammary gland may be particularly vulnerable obesogens, scarcity research investigating obesogen-mediated changes adipocytes drive oncogenic transformation cells. Here, we review preclinical clinical evidence linking DDT impaired development risk. We discuss how obesogen-driven mechanisms obesity, secretion, could provide pro-inflammatory, nutrient-rich environment promotes activation pathways Understanding role obesogens risk progression essential for informing public health guidelines aimed at minimizing obesogen exposure, ultimately reduce improve outcomes women.

Язык: Английский

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Effect of palliative radiotherapy and cyclin-dependent kinase 4/6 inhibitor on breast cancer cell lines

Naunyn-Schmiedeberg s Archives of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Март 4, 2025

Язык: Английский

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The Recent Research Progress of NF-κB Signaling on the Proliferation, Migration, Invasion, Immune Escape and Drug Resistance of Glioblastoma

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(12), С. 10337 - 10337

Опубликована: Июнь 19, 2023

Glioblastoma multiforme (GBM) is the most common and invasive primary central nervous system tumor in humans, accounting for approximately 45–50% of all brain tumors. How to conduct early diagnosis, targeted intervention, prognostic evaluation GBM, order improve survival rate glioblastoma patients, has always been an urgent clinical problem be solved. Therefore, a deeper understanding molecular mechanisms underlying occurrence development GBM also needed. Like many other cancers, NF-κB signaling plays crucial role growth therapeutic resistance GBM. However, mechanism high activity remains elucidated. This review aims identify summarize involved recent pathogenesis as well basic therapy via signaling.

Язык: Английский

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From Crypts to Cancer: A Holistic Perspective on Colorectal Carcinogenesis and Therapeutic Strategies

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9463 - 9463

Опубликована: Авг. 30, 2024

Colorectal cancer (CRC) represents a significant global health burden, with high incidence and mortality rates worldwide. Recent progress in research highlights the distinct clinical molecular characteristics of colon versus rectal cancers, underscoring tumor location's importance treatment approaches. This article provides comprehensive review our current understanding CRC epidemiology, risk factors, pathogenesis, management strategies. We also present intricate cellular architecture colonic crypts their roles intestinal homeostasis. carcinogenesis multistep processes are described, covering conventional adenoma-carcinoma sequence, alternative serrated pathways, influential Vogelstein model, which proposes sequential

Язык: Английский

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Oleic acid inhibits the migration and invasion of breast cancer cells with stemness characteristics through oxidative stress-mediated attenuation of the FAK/AKT/NF-κB pathway

Journal of Functional Foods, Год журнала: 2024, Номер 116, С. 106224 - 106224

Опубликована: Май 1, 2024

Oleic acid, found in a variety of food sources, is beneficial to health. However, studies on its anticancer effects cancer stem cells resistant conventional treatments and the mechanisms underlying such are scarce. Here, we evaluated oleic acid against breast with stemness characteristics. inhibited proliferation stem-like more significantly than that their respective parental cells, reduced expression cell markers migration invasion propensity. It also repressed phosphorylation FAK, AKT, NF-κB, proteins involved invasion. acid-induced increase reactive oxygen species levels mediated inhibition FAK/AKT/NF-κB signaling axis. Our study demonstrates oxidative stress plays an important role inhibiting metastatic behavior characteristics relevant for management treatment-resistant cancer.

Язык: Английский

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