The role of IL-6/JAK2/STAT3 signaling pathway in cancers

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Dec. 16, 2022

Interleukin-6 (IL-6) is a pleiotropic cytokine involved in immune regulation. It can activate janus kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway. As one the important signal transduction pathways cells, JAK2/STAT3 pathway plays critical role cell proliferation differentiation by affecting activation state downstream effector molecules. The tumorigenesis development. contributes to formation tumor inflammatory microenvironment closely related occurrence development many human tumors. This article focuses on relationship between IL-6/JAK2/STAT3 liver cancer, breast colorectal gastric lung pancreatic cancer ovarian hoping provide references for research treatment targeting key molecules

Language: Английский

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Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma

Biomedicines, Journal Year: 2022, Volume and Issue: 10(12), P. 3202 - 3202

Published: Dec. 9, 2022

Hepatocellular carcinoma (HCC) is the most frequent liver cancer with high lethality and low five-year survival rates leading to a substantial worldwide burden for healthcare systems. HCC initiation progression are favored by different etiological risk factors including hepatitis B virus (HBV) C (HCV) infection, non-/and alcoholic fatty disease (N/AFLD), tobacco smoking. In molecular pathogenesis, endogenous alteration in genetics (TP53, TERT, CTNNB1, etc.), epigenetics (DNA-methylation, miRNA, lncRNA, dysregulation of key signaling pathways (Wnt/β-catenin, JAK/STAT, etc.) strongly contribute development HCC. The multitude complexity pathomechanisms also reflect difficulties tailored medical therapy Treatment options strictly dependent on tumor staging function, which structured updated Barcelona Clinic Liver Cancer classification system. Surgical resection, local ablative techniques, transplantation valid curative therapeutic early stages. For multifocal metastatic diseases, systemic recommended. While Sorafenib had been standalone first-line decades, recent developments led approval new treatment as well second-line treatment. Anti-PD-L1 directed combination therapies either anti-VEGF agents or anti-CTLA-4 active substances have implemented standard setting. However, data from clinical trials indicate responses specific regimens depending underlying pathogenesis hepatocellular cancer. Therefore, histopathological examinations re-emphasized current international guidelines addition standardized radiological diagnosis using contrast-enhanced cross-sectional imaging. this review, we emphasize knowledge carcinoma. On occasion, sequences advanced stages according recently system algorithm (first-, second-, third-line treatment) summarized. Furthermore, discuss novel precautional pre-therapeutic approaches vaccination, adoptive cell transfer, locoregional enhancement, non-coding RNA-based promising options. These treatments may prolong overall regard quality life function mainstay therapy.

Language: Английский

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JAK: Not Just Another Kinase

Molecular Cancer Therapeutics, Journal Year: 2022, Volume and Issue: 21(12), P. 1757 - 1764

Published: Oct. 17, 2022

Abstract The JAK/STAT axis is implicated in cancer, inflammation, and immunity. Numerous cytokines/growth factors affect signaling. JAKs (JAK1, JAK2, JAK3, TYK2) noncovalently associate with cytokine receptors, mediate receptor tyrosine phosphorylation, recruit ≥1 STAT proteins (STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, STAT6). Tyrosine-phosphorylated STATs dimerize are then transported into the nucleus to function as transcription factors. Signaling attenuated by specific suppressor of signaling proteins, creating a negative feedback loop. Both germline mutations polymorphisms JAK family members correlate diseases: Systemic lupus erythematosus (TYK2 polymorphisms); severe combined immunodeficiency (JAK3 mutations); pediatric acute lymphoblastic leukemia hereditary thrombocytosis (JAK2 mutations). Somatic gain-of-function mainly occur hematologic malignancies, activating JAK2 V617F being myeloproliferative disorder hallmark; it also seen clonal hematopoiesis indeterminate potential. Several T-cell well B-cell leukemia, megakaryoblastic harbor somatic alterations. On other hand, copy-number loss associated immune checkpoint inhibitor resistance. inhibitors (jakinibs) have been deployed many conditions activation; they approved disorders, rheumatoid psoriatic arthritis, atopic dermatitis, ulcerative colitis, graft-versus-host disease, alopecia areata, ankylosing spondylitis, patients hospitalized for COVID-19. Clinical trials investigating jakinibs multiple autoimmune/inflammatory conditions. Furthermore, dermatologic neurologic improvements observed children Aicardi–Goutieres syndrome (a genetic interferonopathy) treated inhibitors.

Language: Английский

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Apigenin: A Therapeutic Agent for Treatment of Skin Inflammatory Diseases and Cancer

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(2), P. 1498 - 1498

Published: Jan. 12, 2023

The skin is the main barrier between body and environment, protecting it from external oxidative stress induced by ultraviolet rays. It also prevents entrance of infectious agents such as viruses, antigens, allergens, bacteria into our bodies. An overreaction to these causes severe diseases, including atopic dermatitis, pruritus, psoriasis, cancer, vitiligo. Members flavonoid family include apigenin, quercetin, luteolin, kaempferol. Of these, apigenin has been used a dietary supplement due its various biological activities shown reduce inflammation downregulating inflammatory markers molecular targets. In this review, we deal with current knowledge about reactions in mechanisms which reduces inflammation.

Language: Английский

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Curcumin-loaded alginate hydrogels for cancer therapy and wound healing applications: A review

International Journal of Biological Macromolecules, Journal Year: 2023, Volume and Issue: 232, P. 123283 - 123283

Published: Jan. 17, 2023

Hydrogels have emerged as a versatile platform for numerous biomedical application due to their ability absorb huge quantity of biofluids. In order design hydrogels, natural polymers are an attractive option owing biocompatibility and biodegradability. Due abundance in occurrence, cost effectiveness, facile crosslinking approaches, alginate has been extensively investigated fabricate hydrogel matrix. Management cancer chronic wounds always challenge pharmaceutical healthcare sector. both cases, curcumin shown significant improvement effectiveness. However, the innate restraints like poor bioavailability, hydrophobicity, rapid systemic clearance associated with restricted its clinical translations. The current review explores cascade research around encapsulated matrix wound healing therapy. focus is emphasize mechanistic effects fate inside cells. Further, discusses different approaches designed loaded hydrogels along parameters that regulates release behavior. Finally, concluded on some key aspect increasing efficacy these novel strategies further develop multifacet applications.

Language: Английский

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miRNAs as potential game-changers in bone diseases: Future medicinal and clinical uses

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 245, P. 154440 - 154440

Published: April 6, 2023

Language: Английский

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JAK-STAT pathway inhibitors in dermatology

Anais Brasileiros de Dermatologia, Journal Year: 2023, Volume and Issue: 98(5), P. 656 - 677

Published: May 23, 2023

The JAK-STAT signaling pathway mediates important cellular processes such as immune response, carcinogenesis, cell differentiation, division and death. Therefore, drugs that interfere with different patterns have potential indications for various medical conditions. main dermatological targets of inhibitors are inflammatory or autoimmune diseases psoriasis, vitiligo, atopic dermatitis alopecia areata; however, several dermatoses under investigation to expand this list indications. As should gradually occupy a relevant space in prescriptions, review presents the available drugs, their immunological effects, pharmacological characteristics, related clinical efficacy safety, aiming validate best practice.

Language: Английский

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Potentials and future perspectives of multi-target drugs in cancer treatment: the next generation anti-cancer agents

Cell Communication and Signaling, Journal Year: 2024, Volume and Issue: 22(1)

Published: April 15, 2024

Abstract Cancer is a major public health problem worldwide with more than an estimated 19.3 million new cases in 2020. The occurrence rises dramatically age, and the overall risk accumulation combined tendency for cellular repair mechanisms to be less effective older individuals. Conventional cancer treatments, such as radiotherapy, surgery, chemotherapy, have been used decades combat cancer. However, emergence of novel fields research has led exploration innovative treatment approaches focused on immunotherapy, epigenetic therapy, targeted multi-omics, also multi-target therapy. hypothesis was based that drugs designed act against individual targets cannot usually battle multigenic diseases like Multi-target therapies, either combination or sequential order, recommended acquired intrinsic resistance anti-cancer treatments. Several studies multi-targeting treatments due their advantages include; overcoming clonal heterogeneity, lower multi-drug (MDR), decreased drug toxicity, thereby side effects. In this study, we'll discuss about drugs, benefits improving recent advances field multi-targeted drugs. Also, we will study performed clinical trials using therapeutic agents treatment.

Language: Английский

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Hepatocellular Carcinoma: Old and Emerging Therapeutic Targets

Cancers, Journal Year: 2024, Volume and Issue: 16(5), P. 901 - 901

Published: Feb. 23, 2024

Liver cancer, predominantly hepatocellular carcinoma (HCC), globally ranks sixth in incidence and third cancer-related deaths. HCC risk factors include non-viral hepatitis, alcohol abuse, environmental exposures, genetic factors. No specific alterations are unequivocally linked to tumorigenesis. Current standard therapies surgical options, systemic chemotherapy, kinase inhibitors, like sorafenib regorafenib. Immunotherapy, targeting immune checkpoints, represents a promising avenue. FDA-approved checkpoint such as atezolizumab pembrolizumab, show efficacy, combination enhance clinical responses. Despite this, the treatment of (HCC) remains challenge, complex tumor ecosystem immunosuppressive microenvironment associated with it hamper efficacy available therapeutic approaches. This review explores current advanced approaches treat HCC, considering both known new potential targets, especially derived from proteomic analysis, which is today considered most approach. Exploring novel strategies, this discusses antibody drug conjugates (ADCs), chimeric antigen receptor T-cell therapy (CAR-T), engineered antibodies. It then reports systematic analysis main ligand/receptor pairs molecular pathways reported be overexpressed cells, highlighting their limitations. Finally, TGFβ, one targets microenvironment.

Language: Английский

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Emerging agents that target signaling pathways to eradicate colorectal cancer stem cells

Cancer Communications, Journal Year: 2021, Volume and Issue: 41(12), P. 1275 - 1313

Published: Nov. 17, 2021

Abstract Colorectal cancer (CRC) represents the third most commonly diagnosed and second leading cause of death worldwide. The modern concept biology indicates that is formed a small population cells called stem (CSCs), which present both pluripotency self‐renewal properties. These are considered responsible for progression disease, recurrence tumor resistance. Interestingly, some cell signaling pathways participate in CRC survival, proliferation, properties, them dysregulated CSCs, including Wingless (Wnt)/β‐catenin, Notch, Hedgehog, nuclear factor kappa B (NF‐κB), Janus kinase/signal transducer activator transcription (JAK/STAT), peroxisome proliferator‐activated receptor (PPAR), phosphatidyl‐inositol‐3‐kinase/Akt/mechanistic target rapamycin (PI3K/Akt/mTOR), transforming growth factor‐β (TGF‐β)/Smad pathways. In this review, we summarize strategies eradicating by modulating these pathways, will contribute to study potential therapeutic schemes, combining conventional drugs with CSC‐targeting drugs, allowing better cure rates anti‐CRC therapy.

Language: Английский

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