Oncogenic STAT Transcription Factors as Targets for Cancer Therapy: Innovative Strategies and Clinical Translation

Cancers, Год журнала: 2024, Номер 16(7), С. 1387 - 1387

Опубликована: Март 31, 2024

Despite advances in our understanding of molecular aspects oncogenesis, cancer remains a leading cause death. The malignant behavior cell is driven by the inappropriate activation transcription factors. In particular, signal transducers and activators (STATs), which regulate many critical cellular processes such as proliferation, apoptosis, differentiation, are frequently activated inappropriately wide spectrum human cancers. Multiple signaling pathways converge on STATs, highlighting their importance development progression oncogenic diseases. STAT3 STAT5 two members STAT protein family that most cancers can drive pathogenesis directly. inhibitors targeting has been subject intense investigations last decade, although effective treatment options remain limited. this review, we investigate specific roles normal physiology biology, discuss opportunities challenges pharmacologically proteins upstream activators, offer insights into novel therapeutic strategies to identify therapeutics.

Язык: Английский

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Osteosarcoma neutrophil extracellular trap network-associated gene recurrence and metastasis model

Journal of Cancer Research and Clinical Oncology, Год журнала: 2024, Номер 150(2)

Опубликована: Янв. 29, 2024

Abstract Osteosarcoma (OS) is the most common malignancy in children and adolescents has a high probability of recurrence metastasis. A growing number studies have shown that neutrophil extracellular traps (NETs) are strongly associated with cancer metastasis, but osteosarcoma, genes NETs promote osteosarcoma metastasis remain to be explored. We systematically investigated gene expression patterns OS samples from GEO database. molecular typing was evaluated based on profiles, association between subtypes immune microenvironment metastatic features were Ultimately, we constructed signature model column line graph prediction screened possible potential drugs for osteosarcoma. established two different NETs, which showed significant differences status, time, tumor microenvironment, biological effects. also NETs-related signature(NRGMS) assess pattern patients predict patients. TOMM40 FH Overall, this study constructs predictive genes, expected provide new insights into

Язык: Английский

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Bioprinting of Cells, Organoids and Organs-on-a-Chip Together with Hydrogels Improves Structural and Mechanical Cues

Cells, Год журнала: 2024, Номер 13(19), С. 1638 - 1638

Опубликована: Окт. 1, 2024

The 3D bioprinting technique has made enormous progress in tissue engineering, regenerative medicine and research into diseases such as cancer. Apart from individual cells, a collection of organoids, can be printed combination with various hydrogels. It hypothesized that will even become promising tool for mechanobiological analyses organoids their matrix environments highly defined precisely structured environments, which the mechanical properties cell environment individually adjusted. Mechanical obstacles or bead markers integrated bioprinted samples to analyze deformations forces within these constructs, perform biophysical analysis complex systems, are still not standard techniques. review highlights advances 4D printing technologies integrating cues so next step detailed key future directions organoid generation development disease model regeneration drug testing perspective. Finally, hydrogels, pure natural synthetic hydrogels mixtures, organoid–cell co-cultures, organ-on-a-chip systems organoid-organ-on-a chip combinations introduces use assembloids determine mutual interactions different types cell–matrix interferences specific biological environments.

Язык: Английский

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Patient-derived organoids of lung cancer based on organoids-on-a-chip: enhancing clinical and translational applications

Frontiers in Bioengineering and Biotechnology, Год журнала: 2023, Номер 11

Опубликована: Май 26, 2023

Lung cancer is one of the most common malignant tumors worldwide, with high morbidity and mortality due to significant individual characteristics genetic heterogeneity. Personalized treatment necessary improve overall survival rate patients. In recent years, development patient-derived organoids (PDOs) enables lung diseases be simulated in real world, closely reflects pathophysiological natural tumor occurrence metastasis, highlighting their great potential biomedical applications, translational medicine, personalized treatment. However, inherent defects traditional organoids, such as poor stability, microenvironment simple components low throughput, limit further clinical transformation applications. this review, we summarized developments applications PDOs discussed limitations transformation. Herein, looked into future proposed that organoids-on-a-chip based on microfluidic technology are advantageous for drug screening. addition, combined advances research, explored value direction precision cancer.

Язык: Английский

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Patient-derived organoids: a promising tool for breast cancer research

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Янв. 26, 2024

Breast cancer (BC) is the most prevalent malignancy among women worldwide. Traditional research models such as primary cell and patient-derived tumor xenografts (PDTXs) have limitations. Cancer cells lack a microenvironment (TME) genetic diversity, whereas PDTXs are expensive time-consuming preparation protocol. Therefore, alternative warranted. Patient-derived organoids (PDOs) promising in vitro model. They mimic TME, gene expression, types of original tissues. PDOs been successfully developed from various cancers, including BC. In this review, we focused on value limitations BC research, their characteristics potential drug development, personalized therapy, immunotherapy, application prospects testing prognosis.

Язык: Английский

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The X-Linked Tumor Suppressor TSPX Regulates Genes Involved in the EGFR Signaling Pathway and Cell Viability to Suppress Lung Adenocarcinoma

Genes, Год журнала: 2025, Номер 16(1), С. 75 - 75

Опубликована: Янв. 11, 2025

Background: TSPX is an X-linked tumor suppressor that was initially identified in non-small cell lung cancer (NSCLC) lines. However, its expression patterns and downstream mechanisms NSCLC remain unclear. This study aims to investigate the functions of by identifying potential targets their correlation with clinical outcomes. Methods: RNA-seq transcriptome pathway enrichment analyses were conducted on TSPX-overexpressing lines, A549 SK-MES-1, originating from adenocarcinoma squamous carcinoma subtypes, respectively. In addition, comparative performed using data specimens (515 adenocarcinomas 502 carcinomas) Cancer Genome Atlas (TCGA) database. Results: TCGA analysis revealed significant downregulation tumors compared adjacent non-cancerous tissues (Wilcoxon matched pairs signed rank test p < 0.0001). Notably, levels inversely correlated stage, higher associated better outcomes improved survival adenocarcinoma, a subtype (median extended 510 days; log-rank test, = 0.0025). lines regulates various genes involved cancer-related signaling pathways viability, consistent suppression proliferation culture assays. patient (log-rank 0.016 4.3 × 10−10) identified, including EGFR pathway-related AREG, EREG, FOSL1, MYC, which downregulated. Conclusions: Our results suggest plays critical role suppressing progression downregulating pro-oncogenic genes, particularly those pathway, upregulating suppressors, especially adenocarcinoma. These findings biomarker therapeutic target for management.

Язык: Английский

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Tumor Microenvironment Dynamics of Triple-Negative Breast Cancer Under Radiation Therapy

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(6), С. 2795 - 2795

Опубликована: Март 20, 2025

Triple-negative breast cancer (TNBC) is an aggressive subtype of characterized by the absence estrogen receptors (ER), progesterone (PR), and HER2 expression. While TNBC relatively less common, accounting for only 10–15% initial diagnosis, due to its nature, it carries a worse prognosis in comparison hormone receptor-positive counterparts. Despite significant advancements screening, treatment cancer, remains important public health burden. Following with chemotherapy, surgery, radiation, over 40% patients experience relapse within 3 years achieve least benefit from post-mastectomy radiation. The tumor microenvironment environment (TME) pivotal initiation, progression, immune evasion, resistance, prognosis. TME complex network that consists cells, non-immune soluble factors located region adjacent modulates therapeutic response differentially between TNBC. mechanisms underlying radiation resistance remain unclear, immunosuppressive has been implicated chemotherapeutic resistance. Radiation therapy (RT) known alter TME; however, changes elicited are poorly date, whether these contribute unknown. This review delves into distinct characteristics TME, explores how RT influences dynamics, examines radiosensitization, radioresistance, responses.

Язык: Английский

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Preclinical Models of Neuroblastoma—Current Status and Perspectives

Cancers, Год журнала: 2023, Номер 15(13), С. 3314 - 3314

Опубликована: Июнь 23, 2023

Preclinical in vitro and vivo models remain indispensable tools cancer research. These classic models, including two- three-dimensional cell culture techniques animal are crucial for basic translational studies. However, each model has its own limitations typically does not fully recapitulate the course of human disease. Therefore, there is an urgent need development novel, advanced systems that can allow efficient evaluation mechanisms underlying progression, more accurately reflect disease pathophysiology complexity, effectively inform therapeutic decisions patients. especially important rare cancers, such as neuroblastoma, where availability patient-derived specimens could be used potential therapy screening limited. Neuroblastoma modeling further complicated by heterogeneity. In this review, we present current status preclinical neuroblastoma research, discuss their characteristics emphasizing strengths limitations, describe necessity clinically relevant approaches.

Язык: Английский

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Xenografting Human Musculoskeletal Sarcomas in Mice, Chick Embryo, and Zebrafish: How to Boost Translational Research

Biomedicines, Год журнала: 2024, Номер 12(8), С. 1921 - 1921

Опубликована: Авг. 21, 2024

Musculoskeletal sarcomas pose major challenges to researchers and clinicians due their rarity heterogeneity. Xenografting human cells or tumor fragments in rodents is a mainstay for the generation of cancer models preclinical trial novel drugs. Lately, though, technical, intrinsic ethical concerns together with stricter regulations have significantly curbed employment murine patient-derived xenografts (mPDX). In alternatives PDXs, focused on embryonal systems such as chorioallantoic membrane (CAM) zebrafish embryos. These are time- cost-effective hosts near-patient cells. The CAM chick embryo represents unique vascularized environment host high engraftment rates, allowing ease visualization molecular detection metastatic Thanks transparency larvae, allow tracking development metastatization, enabling high-throughput drug screening. This review will focus xenograft musculoskeletal highlight technically distinctive features different hosts, how they can be exploited elucidate biological mechanisms beneath phases tumor's natural history development. Ultimately, suggests combination an advantageous approach boost basic translational research.

Язык: Английский

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Lipocalin-2 promotes breast cancer brain metastasis by enhancing tumor invasion and modulating brain microenvironment

Frontiers in Oncology, Год журнала: 2024, Номер 14

Опубликована: Авг. 12, 2024

Breast cancer is the leading diagnosed in women globally, with brain metastasis emerging as a major cause of death, particularly human epidermal growth factor receptor 2 positive and triple-negative breast subtypes. Comprehensive understanding molecular foundations central nervous system metastases imperative for evolution efficacious treatment strategies. Lipocalin-2 (LCN2), secreted iron transport protein multiple functions, has been linked to progression (BCBM). In primary tumors, LCN2 promotes proliferation angiogenesis cells, triggers epithelial-mesenchymal transition, interacts matrix metalloproteinase-9, thereby facilitating reorganization extracellular enhancing cell invasion migration. microenvironment, undermines blood-brain barrier facilitates tumor seeding by modulating behavior key cellular components. summary, this review meticulously examines fuel role BCBM cascade, investigates potential mechanisms involved. It highlights both therapeutic target biomarker, indicating that interventions targeting may offer improved outcomes patients afflicted BCBM.

Язык: Английский

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