Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments
Gliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies...
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| Aineistotyyppi: | Artikkeli |
| Kieli: | English |
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Frontiers Media S.A.
2021-05-01
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| Sarja: | Frontiers in Pharmacology |
| Aiheet: | |
| Linkit: | https://www.frontiersin.org/articles/10.3389/fphar.2021.680021/full |
| _version_ | 1828822494291689472 |
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| author | Mahmoud S. Alghamri Mahmoud S. Alghamri Brandon L. McClellan Brandon L. McClellan Carson S. Hartlage Carson S. Hartlage Santiago Haase Santiago Haase Syed Mohd Faisal Syed Mohd Faisal Rohit Thalla Rohit Thalla Ali Dabaja Ali Dabaja Kaushik Banerjee Kaushik Banerjee Stephen V. Carney Stephen V. Carney Anzar A. Mujeeb Anzar A. Mujeeb Michael R. Olin Michael R. Olin James J. Moon James J. Moon James J. Moon Anna Schwendeman Anna Schwendeman Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Maria G. Castro Maria G. Castro Maria G. Castro Maria G. Castro |
| author_facet | Mahmoud S. Alghamri Mahmoud S. Alghamri Brandon L. McClellan Brandon L. McClellan Carson S. Hartlage Carson S. Hartlage Santiago Haase Santiago Haase Syed Mohd Faisal Syed Mohd Faisal Rohit Thalla Rohit Thalla Ali Dabaja Ali Dabaja Kaushik Banerjee Kaushik Banerjee Stephen V. Carney Stephen V. Carney Anzar A. Mujeeb Anzar A. Mujeeb Michael R. Olin Michael R. Olin James J. Moon James J. Moon James J. Moon Anna Schwendeman Anna Schwendeman Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Maria G. Castro Maria G. Castro Maria G. Castro Maria G. Castro |
| author_sort | Mahmoud S. Alghamri |
| collection | DOAJ |
| description | Gliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas. |
| first_indexed | 2024-12-12T13:14:56Z |
| format | Article |
| id | doaj.art-d0bcbb33bc1e4b30b99e75b5f849bf8c |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-12T13:14:56Z |
| publishDate | 2021-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-d0bcbb33bc1e4b30b99e75b5f849bf8c2022-12-22T00:23:26ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-05-011210.3389/fphar.2021.680021680021Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical DevelopmentsMahmoud S. Alghamri0Mahmoud S. Alghamri1Brandon L. McClellan2Brandon L. McClellan3Carson S. Hartlage4Carson S. Hartlage5Santiago Haase6Santiago Haase7Syed Mohd Faisal8Syed Mohd Faisal9Rohit Thalla10Rohit Thalla11Ali Dabaja12Ali Dabaja13Kaushik Banerjee14Kaushik Banerjee15Stephen V. Carney16Stephen V. Carney17Anzar A. Mujeeb18Anzar A. Mujeeb19Michael R. Olin20Michael R. Olin21James J. Moon22James J. Moon23James J. Moon24Anna Schwendeman25Anna Schwendeman26Pedro R. Lowenstein27Pedro R. Lowenstein28Pedro R. Lowenstein29Pedro R. Lowenstein30Maria G. Castro31Maria G. Castro32Maria G. Castro33Maria G. Castro34Department of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Pediatrics, University of Minnesota, Minneapolis, MN, United StatesMasonic Cancer Center, University of Minnesota, Minneapolis, MN, United StatesDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, United StatesBiointerfaces Institute, University of Michigan, Ann Arbor, MI, United StatesDepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI, United StatesDepartment of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, United StatesBiointerfaces Institute, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United StatesBiosciences Initiative in Brain Cancer, University of Michigan, Ann Arbor, MI, United StatesDepartment of Neurosurgery, University of Michigan Medical School, Ann Arbor, MI, United StatesDepartment of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI, United StatesRogel Cancer Center, University of Michigan Medical School, Ann Arbor, MI, United StatesBiosciences Initiative in Brain Cancer, University of Michigan, Ann Arbor, MI, United StatesGliomas are one of the most lethal types of cancers accounting for ∼80% of all central nervous system (CNS) primary malignancies. Among gliomas, glioblastomas (GBM) are the most aggressive, characterized by a median patient survival of fewer than 15 months. Recent molecular characterization studies uncovered the genetic signatures and methylation status of gliomas and correlate these with clinical prognosis. The most relevant molecular characteristics for the new glioma classification are IDH mutation, chromosome 1p/19q deletion, histone mutations, and other genetic parameters such as ATRX loss, TP53, and TERT mutations, as well as DNA methylation levels. Similar to other solid tumors, glioma progression is impacted by the complex interactions between the tumor cells and immune cells within the tumor microenvironment. The immune system’s response to cancer can impact the glioma’s survival, proliferation, and invasiveness. Salient characteristics of gliomas include enhanced vascularization, stimulation of a hypoxic tumor microenvironment, increased oxidative stress, and an immune suppressive milieu. These processes promote the neuro-inflammatory tumor microenvironment which can lead to the loss of blood-brain barrier (BBB) integrity. The consequences of a compromised BBB are deleteriously exposing the brain to potentially harmful concentrations of substances from the peripheral circulation, adversely affecting neuronal signaling, and abnormal immune cell infiltration; all of which can lead to disruption of brain homeostasis. In this review, we first describe the unique features of inflammation in CNS tumors. We then discuss the mechanisms of tumor-initiating neuro-inflammatory microenvironment and its impact on tumor invasion and progression. Finally, we also discuss potential pharmacological interventions that can be used to target neuro-inflammation in gliomas.https://www.frontiersin.org/articles/10.3389/fphar.2021.680021/fullimmunosuppressioninflammationtumor microenvironmentgliomaimmunotherapy |
| spellingShingle | Mahmoud S. Alghamri Mahmoud S. Alghamri Brandon L. McClellan Brandon L. McClellan Carson S. Hartlage Carson S. Hartlage Santiago Haase Santiago Haase Syed Mohd Faisal Syed Mohd Faisal Rohit Thalla Rohit Thalla Ali Dabaja Ali Dabaja Kaushik Banerjee Kaushik Banerjee Stephen V. Carney Stephen V. Carney Anzar A. Mujeeb Anzar A. Mujeeb Michael R. Olin Michael R. Olin James J. Moon James J. Moon James J. Moon Anna Schwendeman Anna Schwendeman Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Pedro R. Lowenstein Maria G. Castro Maria G. Castro Maria G. Castro Maria G. Castro Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments Frontiers in Pharmacology immunosuppression inflammation tumor microenvironment glioma immunotherapy |
| title | Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments |
| title_full | Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments |
| title_fullStr | Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments |
| title_full_unstemmed | Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments |
| title_short | Targeting Neuroinflammation in Brain Cancer: Uncovering Mechanisms, Pharmacological Targets, and Neuropharmaceutical Developments |
| title_sort | targeting neuroinflammation in brain cancer uncovering mechanisms pharmacological targets and neuropharmaceutical developments |
| topic | immunosuppression inflammation tumor microenvironment glioma immunotherapy |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.680021/full |
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