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

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: March 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.

Language: Английский

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Cancer stem cells: advances in knowledge and implications for cancer therapy

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: July 5, 2024

Abstract Cancer stem cells (CSCs), a small subset of in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, maintain tumor heterogeneity. continues be significant global disease burden. In the past, surgery, radiotherapy, chemotherapy were main cancer treatments. The technology treatments develop advance, emergence targeted therapy, immunotherapy provides more options for patients certain extent. However, limitations efficacy treatment resistance still inevitable. Our review begins with brief introduction historical discoveries, original hypotheses, pathways regulate CSCs, such as WNT/β-Catenin, hedgehog, Notch, NF-κB, JAK/STAT, TGF-β, PI3K/AKT, PPAR pathway, their crosstalk. We focus on role CSCs various therapeutic outcomes resistance, including how affect content alteration related molecules, CSCs-mediated clinical value targeting refractory, progressed or advanced tumors. summary, efficacy, method is difficult determine. Clarifying regulatory mechanisms biomarkers currently mainstream idea.

Language: Английский

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Apoptosis: A Comprehensive Overview of Signaling Pathways, Morphological Changes, and Physiological Significance and Therapeutic Implications

Cells, Journal Year: 2024, Volume and Issue: 13(22), P. 1838 - 1838

Published: Nov. 6, 2024

Cell survival and death are intricately governed by apoptosis, a meticulously controlled programmed cell death. Apoptosis is vital in facilitating embryonic development maintaining tissue homeostasis immunological functioning. It complex interplay of intrinsic extrinsic signaling pathways that ultimately converges on executing the apoptotic program. The pathway initiated binding ligands such as TNF-α Fas to their respective receptors surface. In contrast, leads increased permeability outer mitochondrial membrane release apoptogenic factors like cytochrome c, which regulated Bcl-2 family proteins. Once activated, these lead cascade biochemical events, including caspase activation, DNA fragmentation, dismantling cellular components. Dysregulation apoptosis implicated various disorders, cancer, autoimmune diseases, neurodegenerative cardiovascular diseases. This article focuses elucidating molecular mechanisms underlying regulation, develop targeted therapeutic strategies. Modulating holds immense potential cancer treatment, where promoting malignant cells could tumor regression. demonstrates targeting providing options for treating neurological illnesses. safety effectiveness apoptosis-targeting drugs being assessed ongoing preclinical clinical trials (phase I-III), opening door more effective approaches better patient outcomes.

Language: Английский

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JAK/STAT in leukemia: a clinical update

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Jan. 26, 2024

Abstract Over the past three decades, considerable efforts have been expended on understanding Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway in leukemia, following identification JAK2V617F mutation myeloproliferative neoplasms (MPNs). The aim this review is to summarize latest progress our involvement JAK/STAT development leukemia. We also attempt provide insights into current use inhibitors leukemia therapy explore pertinent clinical trials field.

Language: Английский

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Kinase Inhibitors and Kinase-Targeted Cancer Therapies: Recent Advances and Future Perspectives

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5489 - 5489

Published: May 17, 2024

Over 120 small-molecule kinase inhibitors (SMKIs) have been approved worldwide for treating various diseases, with nearly 70 FDA approvals specifically cancer treatment, focusing on targets like the epidermal growth factor receptor (EGFR) family. Kinase-targeted strategies encompass monoclonal antibodies and their derivatives, such as nanobodies peptides, along innovative approaches use of degraders protein interaction inhibitors, which recently demonstrated clinical progress potential in overcoming resistance. Nevertheless, kinase-targeted encounter significant hurdles, including drug resistance, greatly impacts benefits patients, well concerning toxicity when combined immunotherapy, restricts full utilization current treatment modalities. Despite these challenges, development remains highly promising. The extensively studied tyrosine family has 70% its stages development, while 30% inadequately explored. Computational technologies play a vital role accelerating novel repurposing existing drugs. Recent FDA-approved SMKIs underscore importance blood-brain barrier permeability long-term patient benefits. This review provides comprehensive summary recent based mechanisms action targets. We summarize latest developments new explore emerging inhibition from perspective. Lastly, we outline obstacles future prospects inhibition.

Language: Английский

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Writers, readers, and erasers RNA modifications and drug resistance in cancer

Molecular Cancer, Journal Year: 2024, Volume and Issue: 23(1)

Published: Aug. 30, 2024

Drug resistance in cancer cells significantly diminishes treatment efficacy, leading to recurrence and metastasis. A critical factor contributing this is the epigenetic alteration of gene expression via RNA modifications, such as N6-methyladenosine (m6A), N1-methyladenosine (m1A), 5-methylcytosine (m5C), 7-methylguanosine (m7G), pseudouridine (Ψ), adenosine-to-inosine (A-to-I) editing. These modifications are pivotal regulating splicing, translation, transport, degradation, stability. Governed by "writers," "readers," "erasers," impact numerous biological processes progression, including cell proliferation, stemness, autophagy, invasion, apoptosis. Aberrant can lead drug adverse outcomes various cancers. Thus, targeting modification regulators offers a promising strategy for overcoming enhancing efficacy. This review consolidates recent research on role prevalent resistance, with focus m6A, m1A, m5C, m7G, Ψ, A-to-I Additionally, it examines regulatory mechanisms linked underscores existing limitations field.

Language: Английский

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Hepatocellular carcinoma: signaling pathways and therapeutic advances

Signal Transduction and Targeted Therapy, Journal Year: 2025, Volume and Issue: 10(1)

Published: Feb. 6, 2025

Abstract Liver cancer represents a major global health concern, with projections indicating that the number of new cases could surpass 1 million annually by 2025. Hepatocellular carcinoma (HCC) constitutes around 90% liver and is primarily linked to factors incluidng aflatoxin, hepatitis B (HBV) C (HCV), metabolic disorders. There are no obvious symptoms in early stage HCC, which often leads delays diagnosis. Therefore, HCC patients usually present tumors advanced incurable stages. Several signaling pathways dis-regulated cause uncontrolled cell propagation, metastasis, recurrence HCC. Beyond frequently altered therapeutically targeted receptor tyrosine kinase (RTK) involved differentiation, telomere regulation, epigenetic modification stress response also provide therapeutic potential. Investigating key their inhibitors pivotal for achieving advancements management At present, primary approaches (TKI), immune checkpoint (ICI), combination regimens. New trials investigating therapies involving ICIs TKIs or anti-VEGF (endothelial growth factor) therapies, as well combinations two immunotherapy The outcomes these expected revolutionize across all Here, we here comprehensive review cellular pathways, potential, evidence derived from late-stage clinical discuss concepts underlying earlier trials, biomarker identification, development more effective therapeutics

Language: Английский

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Cardiovascular safety of Janus kinase inhibitors in inflammatory bowel disease: a systematic review and network meta-analysis

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: Jan. 21, 2025

Background and Objective Janus kinase (JAK) inhibitors (JAKinibs) are effective for inflammatory bowel disease (IBD), but their cardiovascular safety is inconclusive. We aim to assess the risks associated with JAKinibs in IBD patients.

Language: Английский

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Tailoring traditional Chinese medicine in cancer therapy

Molecular Cancer, Journal Year: 2025, Volume and Issue: 24(1)

Published: Jan. 21, 2025

Language: Английский

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The JAK-STAT pathway: from structural biology to cytokine engineering

Signal Transduction and Targeted Therapy, Journal Year: 2024, Volume and Issue: 9(1)

Published: Aug. 21, 2024

Abstract The Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway serves as a paradigm for signal transduction from the extracellular environment to nucleus. It plays pivotal role in physiological functions, such hematopoiesis, immune balance, tissue homeostasis, surveillance against tumors. Dysregulation this may lead various disease conditions deficiencies, autoimmune diseases, hematologic disorders, cancer. Due its critical maintaining human health involvement disease, extensive studies have been conducted on pathway, ranging basic research medical applications. Advances structural biology enabled us gain insights into how signaling cascade operates at molecular level, laying groundwork therapeutic development targeting pathway. Various strategies developed restore normal function, with promising potential. Enhanced comprehension these mechanisms, combined advances protein engineering methodologies, has allowed engineer cytokines tailored properties targeted applications, thereby enhancing their efficiency safety. In review, we outline basis that governs key nodes offering comprehensive overview process. Furthermore, explore recent cytokine

Language: Английский

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