Targeting triple negative breast cancer stem cells using nanocarriers

Discover Nano, Journal Year: 2024, Volume and Issue: 19(1)

Published: March 7, 2024

Abstract Breast cancer is a complex and heterogeneous disease, encompassing various subtypes characterized by distinct molecular features, clinical behaviors, treatment responses. Categorization of based on the presence or absence estrogen receptor (ER), progesterone (PR), human epidermal growth factor 2 (HER2), leading to such as luminal A, B, HER2-positive, triple-negative breast (TNBC). TNBC, comprising around 20% all cancers, lacks expression ER, PR, HER2 receptors, rendering it unresponsive targeted therapies presenting significant challenges in treatment. TNBC associated with aggressive behavior, high rates recurrence, resistance chemotherapy. Tumor initiation, progression, are attributed stem cells (BCSCs), which possess self-renewal, differentiation, tumorigenic potential. Surface markers, self-renewal pathways (Notch, Wnt, Hedgehog signaling), apoptotic protein (Bcl-2), angiogenesis inhibition (VEGF inhibitors), immune modulation (cytokines, checkpoint inhibitors) among key targets discussed this review. However, targeting BCSC subpopulation presents challenges, including off-target effects, low solubility, bioavailability anti-BCSC agents. Nanoparticle-based offer promising approach target cellular processes implicated survival BSCS TNBC. In review, we explore nanocarrier-based approaches for BCSCs aiming overcome these improve outcomes patients. These nanoparticle-based therapeutic strategies hold promise addressing gap delivering while minimizing systemic toxicity enhancing efficacy. Graphical abstract

Language: Английский

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HMGA2 regulation by miRNAs in cancer: Affecting cancer hallmarks and therapy response

Pharmacological Research, Journal Year: 2023, Volume and Issue: 190, P. 106732 - 106732

Published: March 15, 2023

High mobility group A 2 (HMGA2) is a protein that modulates the structure of chromatin in nucleus. Importantly, aberrant expression HMGA2 occurs during carcinogenesis, and this an upstream mediator cancer hallmarks including evasion apoptosis, proliferation, invasion, metastasis, therapy resistance. targets critical signaling pathways such as Wnt/β-catenin mTOR cells. Therefore, suppression function notably decreases progression improves outcome patients. As mainly oncogenic, targeting by non-coding RNAs (ncRNAs) crucial to take into consideration since it affects function. MicroRNAs (miRNAs) belong ncRNAs are master regulators vital cell processes, which affect all aspects hallmarks. Long (lncRNAs) circular (circRNAs), other members ncRNAs, mediators miRNAs. The current review intends discuss importance miRNA/HMGA2 axis modulation various types cancer, mentions lncRNAs circRNAs, regulate mediators. Finally, we effect miRNAs interactions on response cells therapy. Regarding role regulation cells, considering confirmed interaction between one miRNAs, promising could be subject future clinical trial experiments.

Language: Английский

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Lysine lactylation (Kla) might be a novel therapeutic target for breast cancer

BMC Medical Genomics, Journal Year: 2023, Volume and Issue: 16(1)

Published: Nov. 10, 2023

Abstract Background Histone lysine lactylation ( Kla ) is a newly identified histone modification, which plays crucial role in cancer progression. Hence, we determined the prognostic value of breast (BC). Methods We obtained RNA expression profiles BC from The Cancer Genome Atlas (TCGA), following screening out Kla-specific genes. Furthermore, by constructing cox model based on Subsequently, lactate accumulation-related genes and through Human Protein HPA ), further performed correlation analysis their expression. Meanwhile, explored effects tumor microenvironment (TME), drug therapy immunotherapy. Moreover, predicted pathways influenced via gene set enrichment (GSEA). Results A total 1073 samples 112 normal controls were TCGA, 23 removed owing to inadequate clinical information. 257 differentially expressed DEKlaG s) BC. involved with CCR7 , IGFBP6 NDUFAF6 OVOL1 SDC1 was established, risk score could be visualized as an independent biomarker for remarkably associated immune microenvironment, related activation various BC-related KEGG pathways. Conclusion In conclusion, contributes resistance undesirable responses, prognosis, suggesting that expected new therapeutic target

Language: Английский

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BARX1 repressed FOXF1 expression and activated Wnt/β-catenin signaling pathway to drive lung adenocarcinoma

International Journal of Biological Macromolecules, Journal Year: 2024, Volume and Issue: 261, P. 129717 - 129717

Published: Jan. 28, 2024

Language: Английский

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Epithelial–mesenchymal plasticity in cancer: signaling pathways and therapeutic targets

MedComm, Journal Year: 2024, Volume and Issue: 5(8)

Published: Aug. 1, 2024

Abstract Currently, cancer is still a leading cause of human death globally. Tumor deterioration comprises multiple events including metastasis, therapeutic resistance and immune evasion, all which are tightly related to the phenotypic plasticity especially epithelial–mesenchymal (EMP). cells with EMP manifest in three states as transition (EMT), partial EMT, mesenchymal–epithelial transition, orchestrate switch heterogeneity tumor via transcriptional regulation series signaling pathways, transforming growth factor‐β, Wnt/β‐catenin, Notch. However, due complicated nature EMP, diverse process not fully understood. In this review, we systematically conclude biological background, regulating mechanisms well role therapy response. We also summarize range small molecule inhibitors, immune‐related approaches, combination therapies that have been developed target for outstanding EMP‐driven deterioration. Additionally, explore potential technique EMP‐based mechanistic investigation research, may burst vigorous prospects. Overall, elucidate multifaceted aspects progression suggest promising direction treatment based on targeting EMP.

Language: Английский

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Protein Coronation-Induced Cancer Staging-Dependent Multilevel Cytotoxicity: An All-Humanized Study in Blood Vessel Organoids

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

The protein corona effect refers to the phenomenon wherein nanomaterials in bloodstream are coated by serum proteins, yet how coronated interact with blood vessels and its toxicity implications remain poorly understood. In this study, we investigated corona-related vessel using an all-humanized assay integrating organoids patient-derived serum. Initially, screened various discern parameters including size, morphology, hydrophobicity, surface charge, chirality-dependent difference influence their uptake organoids. For showing substantial differences uptake, was analyzed label-free mass spectra. Our findings revealed involvement of cancer staging-related cytoskeleton components mediating preferential cells, endothelial mural cells. Additionally, a transcriptome study conducted elucidate nanomaterials. We confirmed that provoke remodeling at both transcriptional translational levels, impacting pathways such as PI3K-Akt/Hippo/Wnt, membraneless organelle integrity, respectively. further demonstrated potential can be harnessed synergize antiangiogenesis therapeutics improve outcomes. anticipate will provide guidance for safe use nanomedicine future.

Language: Английский

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Periostin-mediated NOTCH1 activation between tumor cells and HSCs crosstalk promotes liver metastasis of small cell lung cancer

Journal of Experimental & Clinical Cancer Research, Journal Year: 2025, Volume and Issue: 44(1)

Published: Jan. 7, 2025

Abstract Background Metastasis is the primary cause of mortality in small cell lung cancer (SCLC), with liver being a predominant site for distal metastasis. Despite this clinical significance, mechanisms underlying interaction between SCLC and microenvironment, fostering metastasis, remain unclear. Methods patient tissue array, bioinformatics analysis were performed to demonstrate role periostin (POSTN) progression, prognosis. Cell migration, invasion sphere formation assay determine oncogenic POSTN. RNA sequencing was utilized identify key signaling pathway regulated by Immunoprecipitation, immunofluorescence co-culture system used clarify mechanism POSTN-NOTCH1 axis tumor cells-hepatic stellate cells (HSCs) crosstalk. Subcutaneous xenograft model metastasis established examine anti-tumor growth metastases effect targeting axis. Results Elevated expression POSTN correlated accelerated progression Conditioned medium rich derived from tumors demonstrates ability activate HSCs microenvironment. Mechanistically, emerges as binding partner membrane receptor NOTCH1 transducing extracellular signals intracellular fibroblasts. Furthermore, proves effective suppressing inhibiting This study elucidates that SCLC-derived secreted protein interacts on promote activation HSCs, thereby providing favorable microenvironment Conclusion These findings uncover intricate communications mediated context Consequently, promising therapeutic strategy metastatic SCLC.

Language: Английский

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Discovery of a DNA repair-associated radiosensitivity index for predicting radiotherapy efficacy in breast cancer

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: March 25, 2025

Purpose Radiotherapy is a cornerstone of breast cancer (BRCA) treatment. Accurately predicting tumor radiosensitivity critical for optimizing therapeutic outcomes and personalizing treatment strategies. DNA repair pathways are key determinants radiotherapy response. Thus, we aimed to develop novel repair-related model identify potential targets enhancing efficacy. Methods A retrospective study was conducted using data from 942 BRCA patients TCGA database. model, comprising index, developed LASSO regression analysis. Patients were stratified into radiosensitive (RS) radioresistant (RR) groups based on their index (RSI). Associations between the RSI, clinicopathological parameters, PD-L1 status analyzed. The CIBERSORT ESTIMATE algorithms employed characterize immune landscape microenvironment. Tumor Immune Dysfunction Exclusion (TIDE) algorithm pRRophetic platform used predict responses. Key genes identified in further validated vitro qRT-PCR experiments. Results We successfully constructed incorporating 10 genes. RS group exhibited significantly better prognosis compared RR group, but this benefit limited those receiving radiotherapy. This survival associated with signature absent who did not receive displayed distinct molecular profile characterized by enrichment TGF-β signaling protein secretion pathways, potentially contributing enhanced radiosensitivity. Furthermore, increased infiltration cells. Notably, RS-PD-L1-high subgroup demonstrated most favorable highest cell infiltration, highlighting responsiveness immunotherapy. In addition, heightened sensitivity CDK HER2 inhibitors. Conversely, resistance DNA-damaging drugs. These findings supported experiments MCF-7 MCF-7/IR lines, confirming differential expression Conclusion conclusion, established cancer. Our reveals strong association radiosensitivity, antitumor immunity, immunotherapy benefit, particularly within subgroup.

Language: Английский

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Wnt signaling in cancer: from biomarkers to targeted therapies and clinical translation

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

Published: April 2, 2025

The Wnt signaling pathway plays a crucial role in development and tissue homeostasis, regulating key cellular processes such as proliferation, differentiation, apoptosis. However, its abnormal activation is strongly associated with tumorigenesis, metastasis, resistance to therapy, making it vital target for cancer treatment. This review provides comprehensive insight into the of cancer, examining normal physiological functions, dysregulation malignancies, therapeutic potential. We emphasize importance predicting sensitivity identify biomarkers across various types. Additionally, we address challenges future prospects Wnt-targeted therapies, including biomarker discovery, advancements emerging technologies, their application clinical practice.

Language: Английский

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Potential role of lncRNA LOXL1-AS1 in human cancer development: a narrative review

Translational Cancer Research, Journal Year: 2024, Volume and Issue: 13(4), P. 1997 - 2011

Published: April 1, 2024

Long non-coding RNAs (lncRNAs) are a group of consisting more than 200 nucleotides that widely involved in various physiological and pathobiological processes the body. LncRNA plays crucial role tumorigenesis development with its unique functions, such as playing variety biological malignant tumors cancer-promoting factor or cancer-suppressor factor. Lysyl oxidase-like protein 1-antisense RNA1 (LOXL1-AS1) is novel functional lncRNA recently reported. This article reviews current findings on LOXL1-AS1 cancer, discusses potential clinical significance application prospects, order to provide theoretical basis reference for diagnosis, treatment screening prognostic markers tumors.

Language: Английский

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