Glioma: molecular signature and crossroads with tumor microenvironment

Cancer and Metastasis Reviews, Год журнала: 2021, Номер 41(1), С. 53 - 75

Опубликована: Окт. 23, 2021

Abstract In patients with glioblastoma, the average survival time current treatments is short, mainly due to recurrences and resistance therapy. This insufficient treatment success is, in large parts, tremendous molecular heterogeneity of gliomas, which affects overall prognosis response therapies plays a vital role gliomas’ grading. addition, tumor microenvironment major player for glioma development Active communication between cells local or neighboring healthy immune environment promotes cancerogenic processes contributes establishing stem cells, drives therapy resistance. Besides genetic alterations primary tumor, tumor-released factors, cytokines, proteins, extracellular vesicles, environmental influences like hypoxia provide ability evade host surveillance machinery promote disease progression. Moreover, there increasing evidence that these players affect biological properties gliomas enable inter-cell supports pro-cancerogenic cell properties. Identifying characterizing complex mechanisms are inevitably necessary adapt therapeutic strategies develop novel measures. Here we an update about junctions where constant traffic biomolecules adds complexity management glioblastoma. Graphical abstract

Язык: Английский

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Tumor microenvironment signaling and therapeutics in cancer progression

Cancer Communications, Год журнала: 2023, Номер 43(5), С. 525 - 561

Опубликована: Апрель 2, 2023

Abstract Tumor development and metastasis are facilitated by the complex interactions between cancer cells their microenvironment, which comprises stromal extracellular matrix (ECM) components, among other factors. Stromal can adopt new phenotypes to promote tumor cell invasion. A deep understanding of signaling pathways involved in cell‐to‐cell cell‐to‐ECM is needed design effective intervention strategies that might interrupt these interactions. In this review, we describe microenvironment (TME) components associated therapeutics. We discuss clinical advances prevalent newly discovered TME, immune checkpoints immunosuppressive chemokines, currently used inhibitors targeting pathways. These include both intrinsic non‐autonomous TME: protein kinase C (PKC) signaling, Notch, transforming growth factor (TGF‐β) Endoplasmic Reticulum (ER) stress response, lactate Metabolic reprogramming, cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) Siglec also recent Programmed Cell Death Protein 1 (PD‐1), Cytotoxic T‐Lymphocyte Associated 4 (CTLA4), T‐cell immunoglobulin mucin‐3 (TIM‐3) Lymphocyte Activating Gene 3 (LAG3) checkpoint along with C‐C chemokine receptor (CCR4)‐ class chemokines 22 (CCL22)/ 17 (CCL17), type 2 (CCR2)‐ (C‐C motif) ligand (CCL2), 5 (CCR5)‐ (CCL3) axis TME. addition, review provides a holistic TME as three‐dimensional microfluidic models believed recapitulate original characteristics patient hence may be platform study mechanisms screen for various anti‐cancer therapies. further systemic influences gut microbiota reprogramming treatment response. Overall, comprehensive analysis diverse most critical highlighting newest preclinical studies underlying biology. highlight importance technologies microfluidics lab‐on‐chip research present an overview extrinsic factors, such inhabitant human microbiome, have potential modulate biology drug responses.

Язык: Английский

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Conjugation of Macrophage-Mimetic Microalgae and Liposome for Antitumor Sonodynamic Immunotherapy via Hypoxia Alleviation and Autophagy Inhibition

ACS Nano, Год журнала: 2023, Номер 17(4), С. 4034 - 4049

Опубликована: Фев. 5, 2023

Sonodynamic therapy (SDT) is a noninvasive technique for local antitumor treatment; however, its clinical application often limited by the low tumor accumulation of SDT agents, tumor's hypoxic microenvironment, and cytoprotective effects autophagy. To address these issues, herein we developed surface-engineered chlorella (Chl, green algae) as targeted drug carrier sustainable oxygen supplier (via photosynthesis) significantly improved via hypoxia alleviation well autophagy inhibition chloroquine phosphate. In this design, macrophage membrane was coated onto Chl to form macrophage-mimetic (MChl) increase biocompatibility driven inflammatory-homing membranes. addition, coating on allowed lipid insertion yield β-cyclodextrin (β-CD) modified MChl (CD-MChl). Subsequently, supramolecular conjugates MChl-NP were constructed host–guest interactions between CD-MChl adamantane (ADA)-modified liposome (ADA-NP), anchored went with hand-in-hand tissues co-delivery Chl, hematoporphyrin, phosphate (loaded in ADA-NP). The synergistic achieved oxygenation, SDT, maximally therapeutic efficacy MChl-CQ-HP-NP against melanoma. Tumor rechallenging results revealed that changes microenvironment including alleviation, induced immunogenic cell death, collectively strong immune response memory.

Язык: Английский

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Glioblastoma Microenvironment and Invasiveness: New Insights and Therapeutic Targets

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(8), С. 7047 - 7047

Опубликована: Апрель 11, 2023

Glioblastoma (GBM) is the most common and malignant primary brain cancer in adults. Without treatment mean patient survival approximately 6 months, which can be extended to 15 months with use of multimodal therapies. The low effectiveness GBM therapies mainly due tumor infiltration into healthy tissue, depends on cells’ interaction microenvironment (TME). cells TME involves cellular components such as stem-like cells, glia, endothelial non-cellular extracellular matrix, enhanced hypoxia, soluble factors adenosine, promote GBM’s invasiveness. However, here we highlight role 3D patient-derived glioblastoma organoids cultures a new platform for study modeling In this review, mechanisms involved GBM-microenvironment are described discussed, proposing potential prognosis biomarkers therapeutic targets.

Язык: Английский

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Lipid-based nanoparticles to address the limitations of GBM therapy by overcoming the blood-brain barrier, targeting glioblastoma stem cells, and counteracting the immunosuppressive tumor microenvironment

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 171, С. 116113 - 116113

Опубликована: Янв. 5, 2024

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, characterized by high heterogeneity, strong invasiveness, poor prognosis, and a low survival rate. A broad range of nanoparticles have been recently developed as drug delivery systems for GBM therapy owing to their inherent size effect ability cross blood-brain barrier (BBB). Lipid-based (LBNPs), such liposomes, solid lipid NPs (SLNs), nano-structured carriers (NLCs), emerged promising system treatment because unique size, surface modification possibilities, proven bio-safety. In this review, main challenges current clinical strategies on how novel LBNPs overcome them were explored. The application progress LBNP-based in chemotherapy, immunotherapy, gene recent years systematically reviewed, prospect was discussed.

Язык: Английский

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The tumour microenvironment, treatment resistance and recurrence in glioblastoma

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Июнь 6, 2024

Abstract The adaptability of glioblastoma (GBM) cells, encouraged by complex interactions with the tumour microenvironment (TME), currently renders GBM an incurable cancer. Despite intensive research, many clinical trials, patients rely on standard treatments including surgery followed radiation and chemotherapy, which have been observed to induce a more aggressive phenotype in recurrent tumours. This failure improve is undoubtedly result insufficient models fail incorporate components human brain TME. Research has increasingly uncovered mechanisms tumour-TME that correlate worsened patient prognoses, tumour-associated astrocyte mitochondrial transfer, neuronal circuit remodelling immunosuppression. hijacked TME highly implicated driving therapy resistance, further alterations within resulting from exposure inducing increased growth invasion. Recent developments improving organoid models, aspects TME, are paving exciting future for research drug development GBM, hopes survival growing closer. review focuses GBMs their effect pathology treatment efficiency, look at challenges face sufficiently recapitulating this adaptive

Язык: Английский

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Noninvasive in vivo imaging of macrophages: understanding tumor microenvironments and delivery of therapeutics

Biomarker Research, Год журнала: 2025, Номер 13(1)

Опубликована: Янв. 26, 2025

Abstract Macrophages are pivotal in the body’s defense and response to inflammation. They present significant numbers widely implicated various diseases, including cancer. While molecular histological techniques have advanced our understanding of macrophage biology, their precise function within cancerous microenvironments remains underexplored. Enhancing knowledge macrophages dynamics extracellular vesicles (EVs) cancer development can potentially improve therapeutic management. Notably, also been harnessed deliver drugs. Noninvasive vivo imaging is crucial for investigating intricate cellular processes, comprehending underlying mechanisms tracking cells EVs’ migration, devising macrophage-dependent drug-delivery systems living organisms. Thus, has become an indispensable tool biomedical research. The integration multimodal approaches continued novel contrast agents hold promise overcoming current limitations expanding applications imaging. This study comprehensively reviews several methods labeling modalities, assessing merits drawbacks each approach. review concludes by offering insights into applicability real time monitoring preclinical clinical scenarios.

Язык: Английский

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Molecular Mechanisms of Drug Resistance in Glioblastoma

International Journal of Molecular Sciences, Год журнала: 2021, Номер 22(12), С. 6385 - 6385

Опубликована: Июнь 15, 2021

Glioblastoma multiforme (GBM) is the most common and fatal primary brain tumor, highly resistant to conventional radiation chemotherapy, not amenable effective surgical resection. The present review summarizes recent advances in our understanding of molecular mechanisms therapeutic resistance GBM already known drugs, characteristics glioblastoma cells, barriers that underlie drug resistance. We also discuss progress has been made development new targeted drugs for glioblastoma, as well delivery across blood–brain barrier (BBB) tumor (BBTB).

Язык: Английский

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New Directions in the Therapy of Glioblastoma

Cancers, Год журнала: 2022, Номер 14(21), С. 5377 - 5377

Опубликована: Окт. 31, 2022

Glioblastoma is the most common histologic type of all gliomas and contributes to 57.3% cases. Despite standard management based on surgical resection radiotherapy, it related poor outcome, with a 5-year relative survival rate below 6.9%. In order improve overall outcome for patients, new therapeutic strategies are needed. Herein, we describe current state knowledge novel targeted therapies in glioblastoma. Based recent studies, compared treatment efficacy measured by progression-free patients treated selected potential antitumor drugs. The results application analyzed inhibitors highly variable despite encouraging conclusions previous preclinical studies. This paper focused drugs that target major glioblastoma kinases. As far, some BRAF favorable. Vemurafenib demonstrated long-term clinical trials while combination dabrafenib trametinib improves PFS both vemurafenib alone. There no evidence any MEK inhibitor effective monotherapy. According knowledge, inhibition more advantageous than Moreover, mTOR (especially paxalisib) may be considered particularly important group. Everolimus partial response significant proportion when combined bevacizumab, however its actual role unclear. Neither nintedanib nor pemigatinib were efficient GBM. Among anti-VEGF drugs, bevacizumab monotherapy was well-tolerated option, significantly associated anti-GBM activity recurrent aflibercept pazopanib has not been demonstrated. Apatinib proven tolerable single trial, but research Lenvatinib under trial. Finally, promising from study regorafenib confirmed ongoing randomized AGILE studies conducted so far have provided relatively wide range which at least well tolerated trials. comprehensive understanding molecular biology promises further outcomes patients.

Язык: Английский

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Challenges in glioblastoma immunotherapy: mechanisms of resistance and therapeutic approaches to overcome them

British Journal of Cancer, Год журнала: 2022, Номер 127(6), С. 976 - 987

Опубликована: Июнь 4, 2022

Язык: Английский

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