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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Paclitaxel and docetaxel resistance in prostate cancer: Molecular mechanisms and possible therapeutic strategies

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 160, С. 114392 - 114392

Опубликована: Фев. 15, 2023

Prostate cancer is among most malignant tumors around the world and this urological tumor can be developed as result of genomic mutations their accumulation during progression towards advanced stage. Due to lack specific symptoms in early stages prostate cancer, patients are diagnosed that cells display low response chemotherapy. Furthermore, enhance aggressiveness cells. Docetaxel paclitaxel suggested well-known compounds for chemotherapy they possess a similar function therapy based on inhibiting depolymerization microtubules, impairing balance microtubules subsequent delay cell cycle progression. The aim current review highlight mechanisms docetaxel resistance cancer. When oncogenic factors such CD133 upregulation PTEN tumor-suppressor shows decrease expression, malignancy enhances induce drug resistance. phytochemicals anti-tumor have been utilized suppressing chemoresistance Naringenin lovastatin used enhancing sensitivity. Moreover, nanostructures polymeric micelles nanobubbles delivery decreasing risk development. These subjects highlighted provide new insight reversing

Язык: Английский

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Inhibition of NF-κB signaling unveils novel strategies to overcome drug resistance in cancers

Drug Resistance Updates, Год журнала: 2024, Номер 73, С. 101042 - 101042

Опубликована: Янв. 4, 2024

Drug resistance in cancer remains a major challenge oncology, impeding the effectiveness of various treatment modalities. The nuclear factor-kappa B (NF-κB) signaling pathway has emerged as critical player development drug cells. This comprehensive review explores intricate relationship between NF-κB and cancer. We delve into molecular mechanisms through which activation contributes to against chemotherapeutic agents, targeted therapies, immunotherapies. Additionally, we discuss potential strategies overcome this by targeting signaling, such small molecule inhibitors combination therapies. Understanding multifaceted interactions is crucial for more effective strategies. By dissecting complex network NF-κB, hope shed light on novel therapeutic approaches that can enhance outcomes, ultimately improving prognosis patients. aims provide overview current state knowledge its role resistance, offering insights may guide future research interventions fight

Язык: Английский

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Versatile function of NF-ĸB in inflammation and cancer

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

Опубликована: Июль 16, 2024

Abstract Nuclear factor-kappaB (NF-ĸB) plays a crucial role in both innate and adaptive immune systems, significantly influencing various physiological processes such as cell proliferation, migration, differentiation, survival, stemness. The function of NF-ĸB cancer progression response to chemotherapy has gained increasing attention. This review highlights the inflammation control, biological mechanisms, therapeutic implications treatment. is instrumental altering release inflammatory factors TNF-α, IL-6, IL-1β, which are key regulation carcinogenesis. Specifically, conditions including colitis, upregulation can intensify inflammation, potentially leading development colorectal cancer. Its pivotal extends regulating tumor microenvironment, impacting components macrophages, fibroblasts, T cells, natural killer cells. influences tumorigenesis dampen anti-tumor responses. Additionally, modulates death notably by inhibiting apoptosis ferroptosis. It also dual stimulating or suppressing autophagy cancers. Beyond these functions, controlling stem fostering angiogenesis, metastatic potential through EMT induction, reducing sensitivity radiotherapy. Given its oncogenic capabilities, research focused on products small molecule compounds that suppress NF-ĸB, offering promising avenues for therapy.

Язык: Английский

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Helicobacter pylori and gastric cancer: mechanisms and new perspectives

Journal of Hematology & Oncology, Год журнала: 2025, Номер 18(1)

Опубликована: Янв. 23, 2025

Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as major etiological agent, affecting an estimated 50% of the world's population. There has been rapidly expanding knowledge molecular and pathogenetic mechanisms H. over decades. This review summarizes latest research advances to elucidate underlying infection in gastric carcinogenesis. Our investigation reveals complex network involving STAT3, NF-κB, Hippo, Wnt/β-catenin pathways, which are dysregulated caused by pylori. Furthermore, we highlight role inducing oxidative stress, DNA damage, chronic inflammation, cell apoptosis—key cellular events that pave way for Emerging evidence also suggests effect on tumor microenvironment its possible implications immunotherapy. synthesizes current identifies gaps warrant further investigation. Despite progress our previous development pylori-induced cancer, comprehensive pylori's is crucial advancement prevention treatment strategies. By elucidating these mechanisms, aim provide more in-depth insights study pylori-related cancer.

Язык: Английский

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STAT3 signaling in prostate cancer progression and therapy resistance: An oncogenic pathway with diverse functions

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 158, С. 114168 - 114168

Опубликована: Янв. 3, 2023

The categorization of cancers demonstrates that prostate cancer is the most common malignancy in men and it causes high death annually. Prostate patients are diagnosed mainly via biomarkers such as PSA test show poor prognosis. cells rapidly diffuse into different parts body their metastasis also a reason for death. Current therapies include chemotherapy, surgery radiotherapy well targeted therapy. progression regulated by factors STAT3 signaling among them. Growth cytokines IL-6 can induce shows carcinogenic impact. Activation occurs promotes malignant behavior tumor cells. Induction increases glycolysis proliferation prevents apoptosis. Furthermore, induces EMT mechanism increasing metastasis. stimulates drug resistance limitation current works lack experiment related to role radio-resistance tumor. Calcitriol, capsazepine β-elemonic compounds capable targeting its inhibition In addition natural products, small molecules have been developed

Язык: Английский

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The Gut-Prostate Axis: A New Perspective of Prostate Cancer Biology through the Gut Microbiome

Cancers, Год журнала: 2023, Номер 15(5), С. 1375 - 1375

Опубликована: Фев. 21, 2023

Obesity and a high-fat diet are risk factors associated with prostate cancer, lifestyle, especially diet, impacts the gut microbiome. The microbiome plays important roles in development of several diseases, such as Alzheimer's disease, rheumatoid arthritis, colon cancer. analysis feces from patients cancer by 16S rRNA sequencing has uncovered various associations between altered microbiomes Gut dysbiosis caused leakage bacterial metabolites, short-chain fatty acids lipopolysaccharide results growth. microbiota also play role metabolism androgen which could affect castration-resistant Moreover, men high-risk share specific treatments androgen-deprivation therapy alter manner that favors Thus, implementing interventions aiming to modify lifestyle or altering prebiotics probiotics may curtail From this perspective, "Gut-Prostate Axis" fundamental bidirectional biology should be considered when screening treating patients.

Язык: Английский

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The Efficacy of Tumor Mutation Burden as a Biomarker of Response to Immune Checkpoint Inhibitors

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(7), С. 6710 - 6710

Опубликована: Апрель 4, 2023

Cancer is one of the leading causes death in world; therefore, extensive research has been dedicated to exploring potential therapeutics, including immune checkpoint inhibitors (ICIs). Initially, programmed-death ligand-1 was biomarker utilized predict efficacy ICIs. However, its heterogeneous expression tumor microenvironment, which critical cancer progression, promoted exploration mutation burden (TMB). Research various cancers, such as melanoma and lung cancer, shown an association between high TMB response ICIs, increasing predictive value. failed ICI numerous other cancers. Therefore, future needed analyze variations types establish cutoffs order create a more standardized methodology for using clinically. In this review, we aim explore current on biomarker, discuss approaches overcoming immunoresistance highlight new trends field liquid biopsies, next generation sequencing, chimeric antigen receptor T-cell therapy, personalized vaccines.

Язык: Английский

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Age at diagnosis for lung, colon, breast and prostate cancers: An international comparative study

International Journal of Cancer, Год журнала: 2023, Номер 154(1), С. 28 - 40

Опубликована: Авг. 24, 2023

Abstract Differences in the average age at cancer diagnosis are observed across countries. We therefore aimed to assess international variation median of common cancers worldwide, after adjusting for differences population structure. used IARC's Cancer Incidence Five Continents (CI5) Volume XI database, comprising diagnoses between 2008 and 2012 from population‐based registries 65 calculated crude ages lung, colon, breast prostate each country, then adjusted using indirect standardization. showed that changed by up 10 years standardization, typically increasing low‐ middle‐income countries (LMICs) decreasing high‐income (HICs), given relatively younger older populations, respectively. After range was 12 lung (median 61‐Bulgaria vs 73‐Bahrain), colon (60‐the Islamic Republic Iran 72‐Peru), female (49‐Algeria, Iran, Korea 59‐USA others) (65‐USA, Lithuania 75‐Philippines). Compared HICs, populations LMICs were diagnosed with but (both p LMICS‐vs‐HICs < 0.001). In higher smoking prevalence, both women men corr Female tended be East Asia, Middle Africa. Our findings suggest worldwide likely reflect population‐level risk factors control measures, including screening.

Язык: Английский

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Malignant function of nuclear factor-kappaB axis in prostate cancer: Molecular interactions and regulation by non-coding RNAs

Pharmacological Research, Год журнала: 2023, Номер 194, С. 106775 - 106775

Опубликована: Апрель 17, 2023

Prostate carcinoma is a malignant situation that arises from genomic alterations in the prostate, leading to changes tumorigenesis. The NF-κB pathway modulates various biological mechanisms, including inflammation and immune responses. Dysregulation of promotes carcinogenesis, increased proliferation, invasion, therapy resistance. As an incurable disease globally, prostate cancer significant health concern, research into genetic mutations function has efficacy facilitate introduction novel therapies. upregulation observed during progression, resulting cell cycle progression proliferation rates. Additionally, endorses resistance death enhances capacity for metastasis, particularly bone metastasis. Overexpression triggers chemoresistance radio-resistance, inhibition by anti-tumor compounds can reduce progression. Interestingly, non-coding RNA transcripts regulate level its nuclear transfer, offering potential avenue modulating

Язык: Английский

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