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      Glioma targeted therapy: insight into future of molecular approaches

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          Abstract

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

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          Proteomics. Tissue-based map of the human proteome.

          Resolving the molecular details of proteome variation in the different tissues and organs of the human body will greatly increase our knowledge of human biology and disease. Here, we present a map of the human tissue proteome based on an integrated omics approach that involves quantitative transcriptomics at the tissue and organ level, combined with tissue microarray-based immunohistochemistry, to achieve spatial localization of proteins down to the single-cell level. Our tissue-based analysis detected more than 90% of the putative protein-coding genes. We used this approach to explore the human secretome, the membrane proteome, the druggable proteome, the cancer proteome, and the metabolic functions in 32 different tissues and organs. All the data are integrated in an interactive Web-based database that allows exploration of individual proteins, as well as navigation of global expression patterns, in all major tissues and organs in the human body. Copyright © 2015, American Association for the Advancement of Science.
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            The 2016 World Health Organization Classification of Tumors of the Central Nervous System: a summary.

            The 2016 World Health Organization Classification of Tumors of the Central Nervous System is both a conceptual and practical advance over its 2007 predecessor. For the first time, the WHO classification of CNS tumors uses molecular parameters in addition to histology to define many tumor entities, thus formulating a concept for how CNS tumor diagnoses should be structured in the molecular era. As such, the 2016 CNS WHO presents major restructuring of the diffuse gliomas, medulloblastomas and other embryonal tumors, and incorporates new entities that are defined by both histology and molecular features, including glioblastoma, IDH-wildtype and glioblastoma, IDH-mutant; diffuse midline glioma, H3 K27M-mutant; RELA fusion-positive ependymoma; medulloblastoma, WNT-activated and medulloblastoma, SHH-activated; and embryonal tumour with multilayered rosettes, C19MC-altered. The 2016 edition has added newly recognized neoplasms, and has deleted some entities, variants and patterns that no longer have diagnostic and/or biological relevance. Other notable changes include the addition of brain invasion as a criterion for atypical meningioma and the introduction of a soft tissue-type grading system for the now combined entity of solitary fibrous tumor / hemangiopericytoma-a departure from the manner by which other CNS tumors are graded. Overall, it is hoped that the 2016 CNS WHO will facilitate clinical, experimental and epidemiological studies that will lead to improvements in the lives of patients with brain tumors.
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              Radiotherapy plus Concomitant and Adjuvant Temozolomide for Glioblastoma

              Glioblastoma, the most common primary brain tumor in adults, is usually rapidly fatal. The current standard of care for newly diagnosed glioblastoma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy plus temozolomide, given concomitantly with and after radiotherapy, in terms of efficacy and safety. Patients with newly diagnosed, histologically confirmed glioblastoma were randomly assigned to receive radiotherapy alone (fractionated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 weeks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (75 mg per square meter of body-surface area per day, 7 days per week from the first to the last day of radiotherapy), followed by six cycles of adjuvant temozolomide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. A total of 573 patients from 85 centers underwent randomization. The median age was 56 years, and 84 percent of patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12.1 months with radiotherapy alone. The unadjusted hazard ratio for death in the radiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P<0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiotherapy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologic toxic effects in 7 percent of patients. The addition of temozolomide to radiotherapy for newly diagnosed glioblastoma resulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity. Copyright 2005 Massachusetts Medical Society.
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                Author and article information

                Contributors
                zhixiongliu@csu.edu.cn
                chengquan@csu.edu.cn
                Journal
                Mol Cancer
                Mol Cancer
                Molecular Cancer
                BioMed Central (London )
                1476-4598
                8 February 2022
                8 February 2022
                2022
                : 21
                : 39
                Affiliations
                [1 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Neurosurgery, , Xiangya Hospital, Central South University, ; Changsha, China
                [2 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, Xiangya School of Medicine, Central South University, ; Changsha, China
                [3 ]GRID grid.216417.7, ISNI 0000 0001 0379 7164, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, ; Changsha, China
                [4 ]GRID grid.410736.7, ISNI 0000 0001 2204 9268, One-Third Lab, College of Bioinformatics Science and Technology, , Harbin Medical University, ; Harbin, China
                [5 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Oncology, , Xiangya Hospital, Central South University, ; Changsha, China
                [6 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Geriatrics, , Xiangya Hospital, Central South University, ; Changsha, China
                [7 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Teaching and Research Section of Clinical Nursing, , Xiangya Hospital of Central South University, ; Changsha, China
                [8 ]GRID grid.452223.0, ISNI 0000 0004 1757 7615, Department of Clinical Pharmacology, , Xiangya Hospital, Central South University, ; Changsha, China
                Author information
                http://orcid.org/0000-0002-0288-6306
                Article
                1513
                10.1186/s12943-022-01513-z
                8822752
                34980141
                bd641f5e-7883-452a-9baf-e4f6a8c7fc59
                © The Author(s) 2022

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 7 November 2021
                : 12 January 2022
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 82073893
                Award ID: 81703622
                Award ID: 82172685
                Award ID: 81873635
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100010031, Postdoctoral Research Foundation of China;
                Award ID: 2018M633002
                Award Recipient :
                Funded by: FundRef http://dx.doi.org/10.13039/501100004735, Natural Science Foundation of Hunan Province;
                Award ID: 2018SK2101
                Award ID: 2018JJ3838
                Award Recipient :
                Funded by: Hunan Provincial Health Committee Foundation
                Award ID: C2019186
                Award Recipient :
                Funded by: Xiangya Hospital Central South University postdoctoral foundation
                Categories
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                © The Author(s) 2022

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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