Targeting cytokine and chemokine signaling pathways for cancer therapy

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

Published: July 22, 2024

Abstract Cytokines are critical in regulating immune responses and cellular behavior, playing dual roles both normal physiology the pathology of diseases such as cancer. These molecules, including interleukins, interferons, tumor necrosis factors, chemokines, growth factors like TGF-β, VEGF, EGF, can promote or inhibit growth, influence microenvironment, impact efficacy cancer treatments. Recent advances targeting these pathways have shown promising therapeutic potential, offering new strategies to modulate system, progression, overcome resistance conventional therapies. In this review, we summarized current understanding implications cytokine chemokine signaling By exploring molecules biology response, highlighted development novel agents aimed at modulating combat The review elaborated on nature cytokines promoters suppressors tumorigenesis, depending context, discussed challenges opportunities presents for intervention. We also examined latest advancements targeted therapies, monoclonal antibodies, bispecific receptor inhibitors, fusion proteins, engineered variants, their metastasis, microenvironment. Additionally, evaluated potential combining therapies with other treatment modalities improve patient outcomes. Besides, focused ongoing research clinical trials that pivotal advancing our application cytokine- chemokine-targeted patients.

Language: Английский

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Oridonin suppresses gastric cancer SGC‐7901 cell proliferation by targeting the TNF‐alpha/androgen receptor/TGF‐beta signalling pathway axis

Journal of Cellular and Molecular Medicine, Journal Year: 2023, Volume and Issue: 27(18), P. 2661 - 2674

Published: July 11, 2023

Statistics provided by GLOBOCAN list gastric cancer as the sixth most common, with a mortality ranking of third highest for year 2020. In China, herb called Rabdosia rubescens (Hemsl.) H.Hara, has been used local residents treatment digestive tract hundreds years. Oridonin, main ingredient herb, curative effect cancer, but mechanism not previously clarified. This study mainly aimed to investigate role TNF-alpha/Androgen receptor/TGF-beta signalling pathway axis in mediating proliferation inhibition oridonin on SGC-7901 cells. MTT assay, cell morphology observation assay and fluorescence were adopted efficacy proliferation. The network pharmacology was predict regulated oridonin. Western blot verify TNF-α/Androgen receptor/TGF-β regulation results showed Oridonin could inhibit cells, change cause nuclear fragmentation. A total 11signaling pathways annotated pharmacology, among them, Tumour necrosis factor alpha (TNF-α) pathway, androgen receptor (AR) transforming growth (TGF-β) account largest proportion. can regulate protein expression three pathways, which is consistent predicted pharmacology. These findings indicated that cells regulating TNF-α /AR /TGF-β axis.

Language: Английский

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Breakthrough of solid tumor treatment: CAR-NK immunotherapy

Cell Death Discovery, Journal Year: 2024, Volume and Issue: 10(1)

Published: Jan. 20, 2024

Language: Английский

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The Role of TGF-β/SMAD Signaling in Hepatocellular Carcinoma: from Mechanism to Therapy and Prognosis

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(4), P. 1436 - 1451

Published: Jan. 1, 2024

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, with high incidence and mortality, accounting for approximately 90% liver cancer.The development HCC a complex process involving abnormal activation or inactivation multiple signaling pathways.Transforming growth factor-β (TGF-β)/Small mothers against decapentaplegic (SMAD) pathway regulates HCC.TGF-β activates intracellular SMADs protein through membrane receptors, resulting in series biological cascades.Accumulating studies have demonstrated that TGF-β/SMAD plays regulatory functions HCC.However, there still controversy about role HCC.Because it involves different pathogenic factors, disease stages, cell microenvironment, as well upstream downstream relationships other pathways.This review will summary mechanism HCC, regulation populations, microenvironments, interaction microRNAs.In addition, we also introduced small molecule inhibitors, therapeutic vaccines, traditional Chinese medicine extracts based on targeting pathway, which provide future research direction therapy pathway.

Language: Английский

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Esculin inhibits hepatic stellate cell activation and CCl4-induced liver fibrosis by activating the Nrf2/GPX4 signaling pathway

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155465 - 155465

Published: Feb. 17, 2024

Language: Английский

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CircRNAs: Pivotal modulators of TGF-β signalling in cancer pathogenesis

Non-coding RNA Research, Journal Year: 2024, Volume and Issue: 9(2), P. 277 - 287

Published: Jan. 26, 2024

The intricate molecular landscape of cancer pathogenesis continues to captivate researchers worldwide, with Circular RNAs (circRNAs) emerging as pivotal players in the dynamic regulation biological functions. study investigates elusive link between circRNAs and Transforming Growth Factor-β (TGF-β) signalling pathway, exploring their collective influence on progression metastasis. Our comprehensive investigation begins by profiling circRNA expression patterns diverse types, revealing a repertoire intricately linked TGF-β pathway. Through integrated bioinformatics analyses functional experiments, we elucidate specific circRNA-mRNA interactions that modulate signalling, unveiling regulatory controls governing this crucial Furthermore, provide compelling evidence impact circRNA-mediated modulation key cellular processes, including epithelial-mesenchymal transition (EMT), migration, cell proliferation. In addition mechanistic roles, have shown promise diagnostic prognostic biomarkers, well potential targets for therapy. Their ability critical pathways, such axis, underscores significance biology clinical applications. interplay is dissected, uncovering novel circuits contribute complexity biology. This review unravels previously unexplored dimension carcinogenesis, emphasizing role shaping landscape.

Language: Английский

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The signaling pathways of traditional Chinese medicine in promoting diabetic wound healing

Journal of Ethnopharmacology, Journal Year: 2021, Volume and Issue: 282, P. 114662 - 114662

Published: Sept. 20, 2021

Language: Английский

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Immunosuppression, immune escape, and immunotherapy in pancreatic cancer: focused on the tumor microenvironment

Cellular Oncology, Journal Year: 2022, Volume and Issue: 46(1), P. 17 - 48

Published: Nov. 11, 2022

Language: Английский

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TGF-β Signaling in Metastatic Colorectal Cancer (mCRC): From Underlying Mechanism to Potential Applications in Clinical Development

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(22), P. 14436 - 14436

Published: Nov. 20, 2022

Colorectal cancer (CRC) is a serious public health issue, and it has the leading incidence mortality among malignant tumors worldwide. CRC patients with metastasis in liver, lung or other distant sites always have poor prognosis. Thus, there an urgent need to discover underlying mechanisms of metastatic colorectal (mCRC) develop optimal therapy for mCRC. Transforming growth factor-β (TGF-β) signaling plays significant role various physiologic pathologic processes, aberrant TGF-β signal transduction contributes mCRC progression. In this review, we summarize alterations pathway patients, functional signaling, its promotion epithelial-mesenchymal transition, facilitation angiogenesis, suppression anti-tumor activity immune cells microenvironment contribution stemness cells. We also discuss possible applications diagnosis, prognosis targeted therapies clinical trials. Hopefully, these research advances will improve development new strategies that can be combined molecular therapy, immunotherapy traditional achieve better efficacy benefit near future.

Language: Английский

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Loss of MLKL ameliorates liver fibrosis by inhibiting hepatocyte necroptosis and hepatic stellate cell activation

Theranostics, Journal Year: 2022, Volume and Issue: 12(11), P. 5220 - 5236

Published: Jan. 1, 2022

Background: Liver fibrosis affects millions of people worldwide without an effective treatment.Although multiple cell types in the liver contribute to fibrogenic process, hepatocyte death is considered be trigger.Multiple forms death, including necrosis, apoptosis, and necroptosis, have been reported co-exist diseases.Mixed lineage kinase domain-like protein (MLKL) terminal effector necroptosis pathway.Although has play important role a number diseases, function MLKL yet unraveled.Methods Results: Here we report that level positively correlated with fibrotic markers samples from both patients animal models.Mlkl deletion mice significantly reduces clinical symptoms CCl4-and bile duct ligation (BDL) -induced injury fibrosis.Further studies indicate Mlkl -/-blocks by reducing hepatic stellate (HSC) activation.AAV8-mediated specific knockdown hepatocytes remarkably alleviates CCl4-induced preventative therapeutic ways.Conclusion: Our results show MLKL-mediated signaling plays damage fibrosis, targeting might way treat fibrosis.

Language: Английский

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