Identification and validation of an anoikis-associated gene signature to predict clinical character, stemness, IDH mutation, and immune filtration in glioblastoma

Frontiers in Immunology, Год журнала: 2022, Номер 13

Опубликована: Авг. 25, 2022

Background Glioblastoma (GBM) is the most prominent and aggressive primary brain tumor in adults. Anoikis a specific form of programmed cell death that plays key role invasion metastasis. The presence anti-anoikis factors associated with aggressiveness drug resistance. Methods non-negative matrix factorization algorithm was used for effective dimension reduction integrated datasets. Differences microenvironment (TME), stemness indices, clinical characteristics between two clusters were analyzed. Difference analysis, weighted gene coexpression network analysis (WGCNA), univariate Cox regression, least absolute shrinkage selection operator regression leveraged to screen prognosis-related genes construct risk score model. Immunohistochemistry performed evaluate expression representative specimens. relationship TME, stemness, traits, immunotherapy response assessed GBM pancancer. Results Two definite identified on basis anoikis-related expression. Patients assigned C1 characterized by shortened overall survival, higher suppressive immune infiltration levels, lower indices. We further constructed scoring model quantify regulatory patterns genes. group poor prognosis, cells differentiated phenotype, whereas exhibited opposite effects. In addition, patients frequency isocitrate dehydrogenase (IDH) mutations more sensitive immunotherapy. Drug sensitivity performed, revealing may benefit from drugs targeting PI3K/mTOR signaling pathway. Conclusion revealed potential relationships features, IDH mutation, elucidated their therapeutic value.

Язык: Английский

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Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

MedComm, Год журнала: 2022, Номер 3(4)

Опубликована: Окт. 5, 2022

Cancer stem cells (CSCs) are defined as a subpopulation of malignant tumor with selective capacities for initiation, self-renewal, metastasis, and unlimited growth into bulks, which believed major cause progressive phenotypes, including recurrence, treatment failure. A number signaling pathways involved in the maintenance cell properties survival CSCs, well-established intrinsic pathways, such Notch, Wnt, Hedgehog signaling, extrinsic vascular microenvironment tumor-associated immune cells. There is also intricate crosstalk between these signal cascades other oncogenic pathways. Thus, targeting pathway molecules that regulate CSCs provides new option therapy-resistant or -refractory tumors. These treatments include small molecule inhibitors, monoclonal antibodies target key well CSC-directed immunotherapies harness systems to CSCs. This review aims provide an overview regulating networks their interactions CSC development. We address update on development therapeutics, special focus those application approval under clinical evaluation.

Язык: Английский

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Promising applications of nanotechnology in inhibiting chemo-resistance in solid tumors by targeting epithelial-mesenchymal transition (EMT)

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 170, С. 115973 - 115973

Опубликована: Дек. 7, 2023

The resistance of cancer cells to chemotherapy, also known as chemo-resistance, poses a significant obstacle treatment and can ultimately result in patient mortality. Epithelial-mesenchymal transition (EMT) is one the many factors processes responsible for chemo-resistance. Studies have shown that targeting EMT help overcome nanotechnology nanomedicine emerged promising approaches achieve this goal. This article discusses potential inhibiting proposes viable strategy combat chemo-resistance various solid tumors, including breast cancer, lung pancreatic glioblastoma, ovarian gastric hepatocellular carcinoma. While has results EMT, further research necessary explore its full overcoming discovering more effective methods future.

Язык: Английский

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Deciphering the Role of Cancer Stem Cells: Drivers of Tumor Evolution, Therapeutic Resistance, and Precision Medicine Strategies

Cancers, Год журнала: 2025, Номер 17(3), С. 382 - 382

Опубликована: Янв. 24, 2025

Cancer stem cells (CSCs) play a central role in tumor progression, recurrence, and resistance to conventional therapies, making them critical focus oncology research. This review provides comprehensive analysis of CSC biology, emphasizing their self-renewal, differentiation, dynamic interactions with the microenvironment (TME). Key signaling pathways, including Wnt, Notch, Hedgehog, are discussed detail highlight potential as therapeutic targets. Current methodologies for isolating CSCs critically examined, addressing advantages limitations advancing precision medicine. Emerging technologies, such CRISPR/Cas9 single-cell sequencing, explored transformative unraveling heterogeneity informing strategies. The also underscores pivotal TME supporting survival, promoting metastasis, contributing resistance. Challenges arising from CSC-driven dormancy analyzed, along strategies mitigate these barriers, novel therapeutics targeted approaches. Ethical considerations integration artificial intelligence designing CSC-specific therapies essential elements future manuscript advocates multi-disciplinary approach that combines innovative advanced therapeutics, collaborative research address complexities CSCs. By bridging existing gaps knowledge fostering advancements personalized medicine, this aims guide development more effective cancer treatment strategies, ultimately improving patient outcomes.

Язык: Английский

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GATAD2B O-GlcNAcylation Regulates Breast Cancer Stem-like Potential and Drug Resistance

Cells, Год журнала: 2025, Номер 14(6), С. 398 - 398

Опубликована: Март 8, 2025

The growth of breast tumors is driven and controlled by a subpopulation cancer cells resembling adult stem cells, which are called stem-like (CSCs). In cancer, the function maintenance CSCs influenced protein O-GlcNAcylation enzyme responsible for this post-translational modification, O-GlcNAc transferase (OGT). However, mechanism regulation OGT cycling in still unclear. Analysis proteome O-GlcNAcome, revealed GATAD2B, component Nucleosome Remodeling Deacetylase (NuRD) complex, as substrate regulated OGT. Reducing GATAD2B genetically impairs mammosphere formation, decreases expression self-renewal factors population. at C-terminus protects from ubiquitination proteasomal degradation cells. We identify ITCH novel E3 ligase show that targeting increases levels phenotypes. Lastly, we overexpression wild-type but not mutant lacking C-terminal sites, promotes drug resistance. Together, key role regulating populations promoting chemoresistance.

Язык: Английский

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Linking Tumor Microenvironment to Plasticity of Cancer Stem Cells: Mechanisms and Application in Cancer Therapy

Frontiers in Oncology, Год журнала: 2021, Номер 11

Опубликована: Июнь 28, 2021

Cancer stem cells (CSCs) are a minority subset of cancer that can drive tumor initiation, promote progression, and induce drug resistance. CSCs difficult to eliminate by conventional therapies eventually mediate relapse metastasis. Moreover, recent studies have shown display plasticity renders them alter their phenotype function. Consequently, the varied phenotypes result in tumorigenesis, dissemination, drug-resistance potential, thereby adding complexity heterogeneity further challenging clinical management cancers. In years, microenvironment (TME) has become hotspot research owing its successful application immunotherapy. Notably, emerging evidence shows TME is involved regulating CSC plasticity. activate stemness pathways immune escape through cytokines exosomes secreted or stromal cells, inducing non-CSCs acquire properties increasing However, relationship between remains poorly understood. this review, we discuss investigations on illustrate underlying mechanisms potential implications suppressing progression We consider review help develop novel therapeutic strategies taking into account interlink

Язык: Английский

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Cancer-associated fibroblasts in non-small cell lung cancer: Recent advances and future perspectives

Cancer Letters, Год журнала: 2021, Номер 514, С. 38 - 47

Опубликована: Май 18, 2021

Язык: Английский

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Chemokines orchestrate tumor cells and the microenvironment to achieve metastatic heterogeneity

Cancer and Metastasis Reviews, Год журнала: 2021, Номер 40(2), С. 447 - 476

Опубликована: Май 6, 2021

Язык: Английский

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BMI1 Silencing Liposomes Suppress Postradiotherapy Cancer Stemness against Radioresistant Hepatocellular Carcinoma

ACS Nano, Год журнала: 2023, Номер 17(23), С. 23405 - 23421

Опубликована: Ноя. 21, 2023

Radiotherapy causes DNA damage by direct ionization and indirect generation of reactive oxygen species (ROS) thereby destroying cancer cells. However, ionizing radiation (IR) unexpectedly elicits metastasis invasion cells inducing stem cells' (CSCs) properties. As BMI1 is a crucial gene that radioresistance an unfavorable prognosis hepatocellular carcinoma (HCC), inhibitor PTC-209 has been encapsulated in ROS-responsive liposome (LP(PTC-209)) to be temporally spatially delivered radioresistant HCC tissue. The ROS generated during IR was not only considered directly cause tumor cell death but also used as stimulator trigger drug release from LP(PTC-209). released into resistant tissue under radiotherapy further led (CSC) differentiation then recovered radiosensitivity tumor. suppression the performance LP(PTC-209) proved on radiosensitive Hepa1-6 CSC models, respectively. Our study clarified relationship between stemness provided insights achieve complete inhibiting stemness.

Язык: Английский

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Circulating tumor cell-derived preclinical models: current status and future perspectives

Cell Death and Disease, Год журнала: 2023, Номер 14(8)

Опубликована: Авг. 17, 2023

Abstract Despite the advancements made in diagnosis and treatment of cancer, stages associated with metastasis remain largely incurable represent primary cause cancer-related deaths. The dissemination cancer is facilitated by circulating tumor cells (CTCs), which originate from or metastatic sites enter bloodstream, subsequently spreading to distant parts body. CTCs have garnered significant attention research due their accessibility peripheral blood, despite low abundance. They are being extensively studied gain a deeper understanding mechanisms underlying identify effective therapeutic strategies for advanced disease. Therefore, substantial efforts been directed towards establishing characterizing relevant experimental models derived CTCs, aiming provide tools research. In this review, we an overview recent progress establishment preclinical CTC-derived models, such as xenografts (CDX) cell cultures, show promise study CTCs. We discuss advantages limitations these conclude summarizing potential future use decisions utility precision medicine tools.

Язык: Английский

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