Ferroptosis in cancer: From molecular mechanisms to therapeutic strategies

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

Опубликована: Март 8, 2024

Ferroptosis is a non-apoptotic form of regulated cell death characterized by the lethal accumulation iron-dependent membrane-localized lipid peroxides. It acts as an innate tumor suppressor mechanism and participates in biological processes tumors. Intriguingly, mesenchymal dedifferentiated cancer cells, which are usually resistant to apoptosis traditional therapies, exquisitely vulnerable ferroptosis, further underscoring its potential treatment approach for cancers, especially refractory cancers. However, impact ferroptosis on extends beyond direct cytotoxic effect cells. induction not only inhibits but also promotes development due negative anticancer immunity. Thus, comprehensive understanding role crucial successful translation therapy from laboratory clinical applications. In this review, we provide overview recent advancements cancer, covering molecular mechanisms, functions, regulatory pathways, interactions with microenvironment. We summarize applications immunotherapy, radiotherapy, systemic therapy, well inhibition various conditions. finally discuss markers, current challenges future directions cancer.

Язык: Английский

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Signaling pathways and targeted therapies for psoriasis

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Ноя. 27, 2023

Abstract Psoriasis is a common, chronic, and inflammatory skin disease with high burden on individuals, health systems, society worldwide. With the immunological pathologies pathogenesis of psoriasis becoming gradually revealed, therapeutic approaches for this have gained revolutionary progress. Nevertheless, mechanisms less common forms remain elusive. Furthermore, severe adverse effects recurrence upon treatment cessation should be noted addressed during treatment, which, however, has been rarely explored integration preliminary findings. Therefore, it crucial to comprehensive understanding behind pathogenesis, which might offer new insights research lead more substantive progress in expand clinical options treatment. In review, we looked briefly introduce epidemiology, subtypes, pathophysiology, comorbidities systematically discuss signaling pathways involving extracellular cytokines intracellular transmission, as well cross-talk between them. discussion, also paid attention potential metabolic epigenetic molecular mechanistic cascades related its comorbidities. This review outlined current psoriasis, especially targeted therapies novel strategies, mechanism recurrence.

Язык: Английский

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

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

Опубликована: Июль 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.

Язык: Английский

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Harnessing the potential of hydrogels for advanced therapeutic applications: current achievements and future directions

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

Опубликована: Июль 1, 2024

The applications of hydrogels have expanded significantly due to their versatile, highly tunable properties and breakthroughs in biomaterial technologies. In this review, we cover the major achievements potential therapeutic applications, focusing primarily on two areas: emerging cell-based therapies promising non-cell modalities. Within context cell therapy, discuss capacity overcome existing translational challenges faced by mainstream therapy paradigms, provide a detailed discussion advantages principal design considerations for boosting efficacy as well list specific examples different disease scenarios. We then explore drug delivery, physical intervention therapies, other areas (e.g., bioadhesives, artificial tissues, biosensors), emphasizing utility beyond mere delivery vehicles. Additionally, complement our latest progress clinical application outline future research directions, particularly terms integration with advanced biomanufacturing This review aims present comprehensive view critical insights into selection both tailored meet requirements diverse diseases situations.

Язык: Английский

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Targeting PI3K/AKT/mTOR and MAPK Signaling Pathways in Gastric Cancer

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(3), С. 1848 - 1848

Опубликована: Фев. 3, 2024

Gastric cancer (GC) is the fourth leading cause of death worldwide, with more than 1 million cases diagnosed every year.

Язык: Английский

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Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches

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

Опубликована: Июль 25, 2024

Abstract Ubiquitination, a pivotal posttranslational modification of proteins, plays fundamental role in regulating protein stability. The dysregulation ubiquitinating and deubiquitinating enzymes is common feature various cancers, underscoring the imperative to investigate ubiquitin ligases deubiquitinases (DUBs) for insights into oncogenic processes development therapeutic interventions. In this review, we discuss contributions ubiquitin–proteasome system (UPS) all hallmarks cancer progress drug discovery. We delve multiple functions UPS oncology, including its regulation cancer-associated pathways, metabolic reprogramming, engagement with tumor immune responses, function phenotypic plasticity polymorphic microbiomes, other essential cellular functions. Furthermore, provide comprehensive overview novel anticancer strategies that leverage UPS, application proteolysis targeting chimeras (PROTACs) molecular glues.

Язык: Английский

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The Role of Curcumin in Cancer: A Focus on the PI3K/Akt Pathway

Cancers, Год журнала: 2024, Номер 16(8), С. 1554 - 1554

Опубликована: Апрель 18, 2024

Cancer is a life-threatening disease and one of the leading causes death worldwide. Despite significant advancements in therapeutic options, most available anti-cancer agents have limited efficacy. In this context, natural compounds with diverse chemical structures been investigated for their multimodal properties. Curcumin polyphenol isolated from rhizomes Curcuma longa has widely studied its anti-inflammatory, anti-oxidant, effects. acts on regulation different aspects cancer development, including initiation, metastasis, angiogenesis, progression. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT) pathway key target therapy, since it implicated proliferation, cell survival. found to inhibit PI3K/Akt tumor cells, primarily via mediators, growth factors, protein kinases, cytokines. This review presents potential curcumin malignancies, such as glioblastoma, prostate breast cancer, head neck cancers, through targeting signaling pathway.

Язык: Английский

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ESM1 enhances fatty acid synthesis and vascular mimicry in ovarian cancer by utilizing the PKM2-dependent warburg effect within the hypoxic tumor microenvironment

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

Опубликована: Май 8, 2024

Abstract Background The hypoxic tumor microenvironment is a key factor that promotes metabolic reprogramming and vascular mimicry (VM) in ovarian cancer (OC) patients. ESM1, secreted protein, plays an important role promoting proliferation angiogenesis OC. However, the of ESM1 VM OC patients has not been determined. Methods Liquid chromatography coupled with tandem MS was used to analyze CAOV3 OV90 cells. Interactions between PKM2, UBA2, SUMO1 were detected by GST pull-down, Co-IP, molecular docking. effects ESM1-PKM2 axis on cell glucose metabolism analyzed based ECAR experiment. biological signaling cells tubule formation, transwell assay, RT‒PCR, Western blot, immunofluorescence, vivo xenograft experiments. Results Our findings demonstrated hypoxia induces upregulation expression through transcription HIF-1α. serves as crucial mediator interaction PKM2 facilitating SUMOylation subsequent formation dimers. This process Warburg effect facilitates nuclear translocation ultimately leading phosphorylation STAT3. These events contribute promotion glycolysis vasculogenic mimicry. Furthermore, our study revealed Shikonin effectively inhibits consequently preventing dimers thereby inhibiting glycolysis, fatty acid synthesis Conclusion increases transcriptional regulation HIF-1α induce dimerization via SUMOylation, which VM.

Язык: Английский

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Therapeutic advances of targeting receptor tyrosine kinases in cancer

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

Опубликована: Авг. 14, 2024

Abstract Receptor tyrosine kinases (RTKs), a category of transmembrane receptors, have gained significant clinical attention in oncology due to their central role cancer pathogenesis. Genetic alterations, including mutations, amplifications, and overexpression certain RTKs, are critical creating environments conducive tumor development. Following discovery, extensive research has revealed how RTK dysregulation contributes oncogenesis, with many subtypes showing dependency on aberrant signaling for proliferation, survival progression. These findings paved the way targeted therapies that aim inhibit crucial biological pathways cancer. As result, RTKs emerged as primary targets anticancer therapeutic Over past two decades, this led synthesis validation numerous small molecule kinase inhibitors (TKIs), now effectively utilized treating various types. In manuscript we provide comprehensive understanding context We explored alterations specific receptors across different malignancies, special dedicated examination current inhibitors, highlighting potential therapies. By integrating latest evidence, seek elucidate pivotal biology efficacy inhibition promising treatment outcomes.

Язык: Английский

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JAM3: A prognostic biomarker for bladder cancer via epithelial–mesenchymal transition regulation

Biomolecules and Biomedicine, Год журнала: 2024, Номер 24(4), С. 897 - 911

Опубликована: Фев. 23, 2024

Understanding the intricate relationship between prognosis, immune function, and molecular markers in bladder cancer (BC) demands sophisticated analytical methods. To identify novel biomarkers for predicting prognosis function BC patients, we combined weighted gene co-expression network analysis (WGCNA) least absolute shrinkage selection operator (LASSO) regression analysis. This was conducted using data from The Cancer Genome Atlas (TCGA) Gene Expression Omnibus (GEO) databases. Ultimately, screened junctional adhesion molecule 3 (JAM3) as an independent risk factor BC. High levels of JAM3 were linked to adverse clinical parameters, such higher T N stages. Additionally, a JAM3-based nomogram model accurately predicted 1-, 3- 5-year survival rates indicating potential utility. Functional enrichment revealed that high expression activated calcium signaling pathway, extracellular matrix (ECM)-receptor interaction, PI3K-Akt positively correlated with genes associated epithelial–mesenchymal transition (EMT). Subsequently, found overexpression promoted migration invasion abilities cells, regulating N-cadherin, metallopeptidase 2 (MMP2), Claudin-1 thereby promoting EMT levels. showed negatively anti-tumor cells CD8+ while pro-tumor M2 macrophages, suggesting its involvement cell infiltration. checkpoint CD200 also positive correlation JAM3. Our findings elevated are predictive poor infiltration patients by process.

Язык: Английский

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