Recent Treatment Strategies and Molecular Pathways in Resistance Mechanisms of Antiangiogenic Therapies in Glioblastoma

Cancers, Год журнала: 2024, Номер 16(17), С. 2975 - 2975

Опубликована: Авг. 27, 2024

Malignant gliomas present great difficulties in treatment, with little change over the past 30 years median survival time of 15 months. Current treatment options include surgery, radiotherapy (RT), and chemotherapy. New therapies aimed at suppressing formation new vasculature (antiangiogenic treatments) or destroying formed tumor (vascular disrupting agents) show promise. This study summarizes existing knowledge regarding processes by which glioblastoma (GBM) tumors acquire resistance to antiangiogenic treatments. The discussion encompasses activation redundant proangiogenic pathways, heightened cell invasion metastasis, induced hypoxia, creation vascular mimicry channels, regulation immune microenvironment. Subsequently, we explore potential strategies overcome this resistance, such as combining other methods, personalizing treatments for each patient, focusing on therapeutic targets, incorporating immunotherapy, utilizing drug delivery systems based nanoparticles. Additionally, would like discuss limitations methods future directions enhance beneficial effects patients GBM. Therefore, review aims research outcome GBM provide a more promising opportunity thoroughly exploring mechanisms investigating novel strategies.

Язык: Английский

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Insights into tumor-derived exosome inhibition in cancer therapy

European Journal of Medicinal Chemistry, Год журнала: 2025, Номер 285, С. 117278 - 117278

Опубликована: Янв. 13, 2025

Язык: Английский

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Targeting PI3K signaling in Lung Cancer: advances, challenges and therapeutic opportunities

Journal of Translational Medicine, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 14, 2025

Abstract Lung cancer remains the leading cause of cancer-related mortality globally, necessitating continual exploration novel therapeutic targets. The phosphoinositide 3-kinase (PI3K) signaling pathway plays a pivotal role in oncogenic processes, including cell growth, survival, metabolism and immune modulation. This comprehensive review delineates distinct roles PI3K subtypes—PI3Kα, PI3Kβ, PI3Kγ PI3Kδ—in lung pathogenesis progression. We evaluate current landscape inhibitors, transitioning from non-selective early-generation compounds to isoform-specific agents, highlighting their clinical efficacy, resistance mechanisms potential combination strategies. Furthermore, intricate interplay between tumor microenvironment is explored, elucidating how modulation can enhance immunotherapeutic responses. Metabolic reprogramming driven by also dissected, revealing vulnerabilities that be therapeutically exploited. Despite promising advancements, challenges such as adverse effects underscore need for personalized medicine approaches development next-generation inhibitors. underscores multifaceted advocates integrated strategies harness its full potential, paving way improved patient outcomes.

Язык: Английский

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PTMs of PD-1/PD-L1 and PROTACs application for improving cancer immunotherapy

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Апрель 4, 2024

Immunotherapy has been developed, which harnesses and enhances the innate powers of immune system to fight disease, particularly cancer. PD-1 (programmed death-1) PD-L1 death ligand-1) are key components in regulation system, context cancer immunotherapy. regulated by PTMs, including phosphorylation, ubiquitination, deubiquitination, acetylation, palmitoylation glycosylation. PROTACs (Proteolysis Targeting Chimeras) a type new drug design technology. They specifically engineered molecules that target specific proteins within cell for degradation. have designed demonstrated their inhibitory activity against PD-1/PD-L1 pathway, showed ability degrade proteins. In this review, we describe how improve efficacy could be novel strategy combine with radiotherapy, chemotherapy immunotherapy patients.

Язык: Английский

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Predictive Biomarkers and Resistance Mechanisms of Checkpoint Inhibitors in Malignant Solid Tumors

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(17), С. 9659 - 9659

Опубликована: Сен. 6, 2024

Predictive biomarkers for immune checkpoint inhibitors (ICIs) in solid tumors such as melanoma, hepatocellular carcinoma (HCC), colorectal cancer (CRC), non-small cell lung (NSCLC), endometrial carcinoma, renal (RCC), or urothelial (UC) include programmed death ligand 1 (PD-L1) expression, tumor mutational burden (TMB), defective deoxyribonucleic acid (DNA) mismatch repair (dMMR), microsatellite instability (MSI), and the microenvironment (TME). Over past decade, several types of ICIs, including cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors, anti-programmed (PD-1) antibodies, anti-lymphocyte activation gene-3 (LAG-3) antibodies have been studied approved by Food Drug Administration (FDA), with ongoing research on others. Recent studies highlight critical role gut microbiome influencing a positive therapeutic response to emphasizing importance modeling factors that can maintain healthy microbiome. However, resistance mechanisms emerge, increased expression alternative checkpoints, T-cell immunoglobulin (Ig), mucin domain-containing 3 (TIM-3), LAG-3, impaired antigen presentation, alterations TME. This review aims synthesize data regarding interactions between microbiota immunotherapy (IT). Understanding these is essential optimizing ICI therapy developing effective combination strategies.

Язык: Английский

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Frontiers in pancreatic cancer on biomarkers, microenvironment, and immunotherapy

Cancer Letters, Год журнала: 2024, Номер unknown, С. 217350 - 217350

Опубликована: Ноя. 1, 2024

Pancreatic cancer remains one of the most challenging malignancies to treat due its late-stage diagnosis, aggressive progression, and high resistance existing therapies. This review examines latest advancements in early detection, therapeutic strategies, with a focus on emerging biomarkers, tumor microenvironment (TME) modulation, integration artificial intelligence (AI) data analysis. We highlight promising including microRNAs (miRNAs) circulating DNA (ctDNA), that offer enhanced sensitivity specificity for early-stage diagnosis when combined multi-omics panels. A detailed analysis TME reveals how components such as cancer-associated fibroblasts (CAFs), immune cells, extracellular matrix (ECM) contribute therapy by creating immunosuppressive barriers. also discuss interventions target these components, aiming improve drug delivery overcome evasion. Furthermore, AI-driven analyses are explored their potential interpret complex data, enabling personalized treatment strategies real-time monitoring response. conclude identifying key areas future research, clinical validation regulatory frameworks AI applications, equitable access innovative comprehensive approach underscores need integrated, outcomes pancreatic cancer.

Язык: Английский

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PTBP3 Mediates IL‐18 Exon Skipping to Promote Immune Escape in Gallbladder Cancer

Advanced Science, Год журнала: 2024, Номер 11(38)

Опубликована: Авг. 8, 2024

Gallbladder cancer (GBC) is the most common malignant tumor of biliary system, with poor response to current treatments. Abnormal alternative splicing has been associated development a variety tumors. Combining GEO database and GBC mRNA-seq analysis, it found high expression factor polypyrimidine region- binding protein 3 (PTBP3) in GBC. Multi-omics analysis revealed that PTBP3 promoted exon skipping interleukin-18 (IL-18), resulting ΔIL-18, an isoform specifically expressed That ΔIL-18 promotes immune escape by down-regulating FBXO38 transcription levels CD8+T cells reduce PD-1 ubiquitin-mediated degradation revealed. Using HuPBMC mouse model, role promoting growth confirmed, showed antisense oligonucleotide blocked production displayed anti-tumor activity. Furthermore, H3K36me3 IL-18 recruiting via MRG15 demonstrated, thereby coupling processes splicing. Interestingly, also H3K36 methyltransferase SETD2 binds hnRNPL, interfering pre-mRNA. Overall, this study provides new insights into how aberrant mechanisms affect escape, potential perspectives for improving immunotherapy.

Язык: Английский

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Peptides as Versatile Regulators in Cancer Immunotherapy: Recent Advances, Challenges, and Future Prospects

Pharmaceutics, Год журнала: 2025, Номер 17(1), С. 46 - 46

Опубликована: Янв. 1, 2025

The emergence of effective immunotherapies has revolutionized therapies for many types cancer. However, current immunotherapy limited efficacy in certain patient populations and displays therapeutic resistance after a period treatment. To address these challenges, growing number drugs have been investigated clinical preclinical applications. diverse functionality peptides made them attractive as modality, the global market peptide-based therapeutics is witnessing significant growth. Peptides can act immunotherapeutic agents treatment malignant cancers. systematic understanding interactions between different host’s immune system remains unclear. This review describes detail roles regulating function cancer immunotherapy. Initially, we systematically elaborate on relevant mechanisms Subsequently, categorize nanomaterials into following three categories: vaccines, anti-cancer peptides, delivery systems. We carefully analyzed overcoming barriers immunotherapy, including multiple strategies to enhance immunogenicity peptide synergistic effect combination with other agents, assemblies functioning stimulators or vehicles deliver agents. Furthermore, introduce status applications discuss weaknesses future prospects materials Overall, this aims comprehension potential lay groundwork research

Язык: Английский

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Ultrasound-Guided Histotripsy Triggers the Release of Tumor-Associated Antigens from Breast Cancers

Cancers, Год журнала: 2025, Номер 17(2), С. 183 - 183

Опубликована: Янв. 8, 2025

Background/Objectives: There is increasing evidence to indicate that histotripsy treatment can enhance the host anti-tumor immune responses both locally at targeting tumor site as well systemically from abscopal effects. Histotripsy a non-invasive ultrasound ablation technology mechanically disrupts target tissue via cavitation. A key factor contributing histotripsy-induced effects believed be release of tumor-specific antigens (TSAs) or tumor-associated (TAAs) induce systemic response. In this study, we studied effect on HER2, well-defined TAA for cancer immunotherapy. Methods: range doses administered HER2-postive mammary cells in an vitro cell culture system and ex vivo were applied. addition, single dose was used murine model. The released proteins, specifically cell-free supernatants pellets analyzed by BCA protein assay, ultra-performance liquid chromatography (UPLC) Western blot. Results: Our results showed could significantly trigger HER2 proteins current study. level actually higher than pellets, suggesting intracellular domain into extracellular compartment. Furthermore, proportionally more doses, indicating free histotripsy-dose-dependent. Conclusions: conclusion, have qualitatively quantitatively demonstrated triggers histotripsy-mediated provides important insights mechanism underlying its immunostimulation suggests potential TSA/TAA-based immunotherapies numerous types.

Язык: Английский

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Advancing brain immunotherapy through functional nanomaterials

Drug Delivery and Translational Research, Год журнала: 2025, Номер unknown

Опубликована: Янв. 9, 2025

Abstract Glioblastoma (GBM), a highly aggressive brain tumor, poses significant treatment challenges due to its immunosuppressive microenvironment and the immune privilege. Immunotherapy activating system T lymphocyte infiltration holds great promise against GBM. However, brain’s low immunogenicity difficulty of crossing blood-brain barrier (BBB) hinder therapeutic efficacy. Recent advancements in immune-actuated particles for targeted drug delivery have shown potential overcome these obstacles. These interact with BBB by rapidly reversibly disrupting structure, thereby significantly enhancing targeting penetrating delivery. The also minimizes long-term damage. At GBM, demonstrated effective chemotherapy, chemodynamic therapy, photothermal therapy (PTT), photodynamic (PDT), radiotherapy, or magnetotherapy, facilitating tumor disruption promoting antigen release. Additionally, components retained autologous tumor-associated antigens presented them dendritic cells (DCs), ensuring prolonged activation. This review explores mechanisms existing strategies, role nanomaterials immunotherapy. We discuss innovative particle-based approaches designed traverse mimicking innate functions improve outcomes tumors. Graphical

Язык: Английский

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