Glioma targeted therapy: insight into future of molecular approaches

Molecular Cancer, Journal Year: 2022, Volume and Issue: 21(1)

Published: Feb. 8, 2022

Gliomas are the common type of brain tumors originating from glial cells. Epidemiologically, gliomas occur among all ages, more often seen in adults, which males susceptible than females. According to fifth edition WHO Classification Tumors Central Nervous System (WHO CNS5), standard care and prognosis can be dramatically different. Generally, circumscribed usually benign recommended early complete resection, with chemotherapy if necessary. Diffuse other high-grade according their molecule subtype slightly intractable, necessity chemotherapy. However, for glioblastoma, feasible resection followed by radiotherapy plus temozolomide define current care. Here, we discuss novel or potential targets treatment gliomas, especially IDH-wild glioblastoma. Classic such as p53 retinoblastoma (RB) pathway epidermal growth factor receptor (EGFR) gene alteration have met failure due complex regulatory network. There is ever-increasing interest immunotherapy (immune checkpoint molecule, tumor associated macrophage, dendritic cell vaccine, CAR-T), microenvironment, combination several efficacious methods. With many targeted therapy options emerging, biomarkers guiding prescription a particular also attractive. More pre-clinical clinical trials urgently needed explore evaluate feasibility corresponding effective personalized options.

Language: Английский

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Immune checkpoint therapy for solid tumours: clinical dilemmas and future trends

Signal Transduction and Targeted Therapy, Journal Year: 2023, Volume and Issue: 8(1)

Published: Aug. 28, 2023

Abstract Immune-checkpoint inhibitors (ICBs), in addition to targeting CTLA-4, PD-1, and PD-L1, novel LAG-3 drugs have also been approved clinical application. With the widespread use of drug, we must deeply analyze dilemma agents seek a breakthrough treatment prospect. Over past decades, these demonstrated dramatic efficacy, especially patients with melanoma non-small cell lung cancer (NSCLC). Nonetheless, field broad concept solid tumours, non-specific indications, inseparable immune response side effects, unconfirmed progressive disease, complex regulatory networks resistance are four barriers that limit its Fortunately, successful trials ICB combination therapies, advent era oncolytic virus gene editing, technical mRNA vaccines nano-delivery systems made remarkable breakthroughs currently. In this review, enumerate mechanisms each checkpoint targets, associations between tumour mutation burden, key or signalling pathways, specific evidence efficacy classical targets new among different types put forward dialectical thoughts on drug safety. Finally, discuss importance accurate triage based recent advances predictive biomarkers diagnostic testing techniques.

Language: Английский

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Immune checkpoint modulators in cancer immunotherapy: recent advances and emerging concepts

Journal of Hematology & Oncology, Journal Year: 2022, Volume and Issue: 15(1)

Published: Aug. 17, 2022

Abstract The discovery of immune checkpoint inhibitors (ICIs) has now been universally acknowledged as a significant breakthrough in tumor therapy after the targeted treatment molecules: anti-programmed cell death protein 1/programmed ligand 1 (PD-1/PD-L1) and anti-cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) on several cancer types achieved satisfying results. However, there are still quite lot patients suffering from severe side effects ineffective outcomes. Although current ICI is far satisfying, series novel molecules with remarkable preclinical clinical benefits being widely investigated, like V-domain Ig suppressor activation (VISTA), which can also be called PD-1 homolog (PD-1H), ectonucleotidases: CD39, CD73, CD38, belong to ribosyl cyclase family, etc. In this review, we systematically summarized discussed these molecules' biological structures, molecular features, corresponding drugs, aiming help in-depth understanding promote practice therapy.

Language: Английский

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Tumor Microenvironment of Hepatocellular Carcinoma: Challenges and Opportunities for New Treatment Options

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(7), P. 3778 - 3778

Published: March 29, 2022

The prevalence of liver cancer is constantly rising, with increasing incidence and mortality in Europe the USA recent decades. Among different subtypes cancers, hepatocellular carcinoma (HCC) most commonly diagnosed cancer. Besides advances diagnosis promising results pre-clinical studies, HCC remains a highly lethal disease. In many cases, an effect chronic inflammation, which leads to formation complex tumor microenvironment (TME) composed immune stromal cells. TME patients challenge for therapies, as it involved metastasis development resistance. However, given that intricate system cells interacting cells, new immune-based therapies are being developed target HCC. Therefore, understanding complexity will provide possibilities design novel more effective immunotherapeutics combinatorial overcome resistance treatment. this review, we describe role inflammation during progression by focusing on TME. We also therapeutic possible treatment options.

Language: Английский

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Tumor-associated macrophages: an effective player of the tumor microenvironment

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: Nov. 16, 2023

Cancer progression is primarily caused by interactions between transformed cells and the components of tumor microenvironment (TME). TAMs (tumor-associated macrophages) make up majority invading immune components, which are further categorized as anti-tumor M1 pro-tumor M2 subtypes. While known to have anti-cancer properties, recognized extend a protective role tumor. As result, manipulates TME in such way that it induces macrophage infiltration switching bias secure its survival. This M2-TAM promotes cancer cell proliferation, neoangiogenesis, lymphangiogenesis, epithelial-to-mesenchymal transition, matrix remodeling for metastatic support, manipulation an immunosuppressive state. additionally promote emergence stem (CSCs), their ability originate, metastasize, relapse into tumors. CSCs also help revealing escape survival strategies during initiation phases. review describes reasons immunotherapy failure and, thereby, devises better impair tumor-TAM crosstalk. study will shed light on understudied TAM-mediated address much-needed holistic approach therapy, encompasses targeting cells, CSCs, all at same time.

Language: Английский

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Revolutionization in Cancer Therapeutics via Targeting Major Immune Checkpoints PD-1, PD-L1 and CTLA-4

Pharmaceuticals, Journal Year: 2022, Volume and Issue: 15(3), P. 335 - 335

Published: March 9, 2022

Numerous research reports have witnessed dramatic advancements in cancer therapeutic approaches through immunotherapy. Blocking immunological checkpoint pathways (mechanisms employed by malignant cells to disguise themselves as normal human body components) has emerged a viable strategy for developing anticancer immunity. Through the development of effective immune inhibitors (ICIs) multiple carcinomas, advances immunity expedited major breakthrough therapy. variety ICIs, such PD-1 (programmed cell death-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) improved system’s efficacy combating cells. Recent studies also supported fact that ICIs combined with other potent antitumor candidates, angiogenic agents, could be solid promising chemopreventive approach improving effectiveness inhibitors. Immune blockade aided antiangiogenesis lowering vascular endothelial growth factor expression alleviating hypoxia. Our review summarized recent clinical improvements blocking tactics, including combinatorial treatment immunogenic death (ICD) inducers which may aid future researchers creating more cancer-fighting strategies.

Language: Английский

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Gamma delta T-cell-based immune checkpoint therapy: attractive candidate for antitumor treatment

Molecular Cancer, Journal Year: 2023, Volume and Issue: 22(1)

Published: Feb. 15, 2023

Abstract As a nontraditional T-cell subgroup, γδT cells have gained popularity in the field of immunotherapy recent years. They extraordinary antitumor potential and prospects for clinical application. Immune checkpoint inhibitors (ICIs), which are efficacious tumor patients, become pioneer drugs since they were incorporated into practice. In addition, that infiltrated tissues found to be state exhaustion or anergy, there is upregulation many immune checkpoints (ICs) on their surface, suggesting similar ability respond ICIs as traditional effector T cells. Studies shown targeting ICs can reverse dysfunctional microenvironment (TME) exert effects by improving γδT-cell proliferation activation enhancing cytotoxicity. Clarification functional TME mechanisms underlying interaction with will solidify combined good treatment option.

Language: Английский

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Identification of a novel cuproptosis-related gene signature and integrative analyses in patients with lower-grade gliomas

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Aug. 15, 2022

Background Cuproptosis is a newly discovered unique non-apoptotic programmed cell death distinguished from known mechanisms like ferroptosis, pyroptosis, and necroptosis. However, the prognostic value of cuproptosis correlation between tumor microenvironment (TME) in lower-grade gliomas (LGGs) remain unknown. Methods In this study, we systematically investigated genetic transcriptional variation, value, expression patterns cuproptosis-related genes (CRGs). The CRG score was applied to quantify subtypes. We then evaluated their values TME, prediction, therapeutic responses LGG. Lastly, collected five paired LGG matched normal adjacent tissue samples Sun Yat-sen University Cancer Center (SYSUCC) verify signature by quantitative real-time PCR (qRT-PCR) Western blotting (WB). Results Two distinct clusters were identified using consensus unsupervised clustering analysis. multilayer alterations with clinical characteristics, prognosis, TME infiltration observed. Then, well-performed risk model (CRG score) developed predict patients’ which validated two external cohorts. classified patients into high- low-risk groups according found that group showed significantly higher survival possibilities than those high-risk ( P <0.001). A high implies scores, more significant infiltration, increased mutation burden. Meanwhile, correlated cancer stem index, chemoradiotherapy sensitivity–related immune checkpoint genes, chemotherapeutic sensitivity, indicating association CRGs treatment responses. Univariate multivariate Cox regression analyses revealed an independent predictor for patients. Subsequently, highly accurate predictive established facilitating application score, showing good ability calibration. Additionally, crucial further qRT-PCR WB. Conclusion Collectively, demonstrated comprehensive overview profiles novel therapy status prognosis. Our findings highlight potential implications CRGs, suggesting may be target

Language: Английский

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Role of hypoxia in cellular senescence

Pharmacological Research, Journal Year: 2023, Volume and Issue: 194, P. 106841 - 106841

Published: June 28, 2023

Senescent cells persist and continuously secrete proinflammatory tissue-remodeling molecules that poison surrounding cells, leading to various age-related diseases, including diabetes, atherosclerosis, Alzheimer's disease. The underlying mechanism of cellular senescence has not yet been fully explored. Emerging evidence indicates hypoxia is involved in the regulation senescence. Hypoxia-inducible factor (HIF)- 1α accumulates under hypoxic conditions regulates by modulating levels markers p16, p53, lamin B1, cyclin D1. Hypoxia a critical condition for maintaining tumor immune evasion, which promoted driving expression genetic factors (such as p53 CD47) while triggering immunosenescence. Under conditions, autophagy activated targeting BCL-2/adenovirus E1B 19-kDa interacting protein 3, subsequently induces p21WAF1/CIP1 well p16Ink4a increases β-galactosidase (β-gal) activity, thereby inducing Deletion p21 gene activity response regulator poly (ADP-ribose) polymerase-1 (PARP-1) level nonhomologous end joining (NHEJ) proteins, repairs DNA double-strand breaks, alleviates Moreover, associated with intestinal dysbiosis an accumulation D-galactose derived from gut microbiota. Chronic leads striking reduction amount Lactobacillus D-galactose-degrading enzymes gut, producing excess reactive oxygen species (ROS) bone marrow mesenchymal stem cells. Exosomal microRNAs (miRNAs) long noncoding RNAs (lncRNAs) play important roles miR-424-5p are decreased hypoxia, whereas lncRNA-MALAT1 increased, both induce present review focuses on recent advances understanding role effects HIFs, PARP-1, microbiota, exosomal mRNA hypoxia-mediated cell specifically discussed. This our provides new clues anti-aging processes treatment aging-related diseases.

Language: Английский

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The interactions of docetaxel with tumor microenvironment

International Immunopharmacology, Journal Year: 2023, Volume and Issue: 119, P. 110214 - 110214

Published: April 29, 2023

Language: Английский

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