Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme

Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy wi...

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Main Authors: Christopher Chin, Emma S. Lunking, Macarena de la Fuente, Nagi G. Ayad
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-11-01
Series:Frontiers in Oncology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fonc.2018.00521/full
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author Christopher Chin
Emma S. Lunking
Macarena de la Fuente
Macarena de la Fuente
Nagi G. Ayad
author_facet Christopher Chin
Emma S. Lunking
Macarena de la Fuente
Macarena de la Fuente
Nagi G. Ayad
author_sort Christopher Chin
collection DOAJ
description Glioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy with Temozolimide (TMZ), and radiation therapy, the current prognosis of GBM patients remains poor, with a median overall survival of 12–15 months (2, 3). Therefore, other treatments are needed to provide better outcomes for GBM patients. Immunotherapy is one of the most promising new cancer treatment approaches. Immunotherapy drugs have obtained regulatory approval in a variety of cancers including melanoma (4), Hodgkin lymphoma (5), and non-small cell lung cancer (6). The basis of immunotherapy in cancer treatment is linked to stimulating the immune system to recognize cancer cells as foreign, thereby leading to the eventual elimination of the tumor. One form of immunotherapy utilizes vaccines that target tumor antigens (7), while other approaches utilize T-cells in patients to stimulate them to attack tumor cells (8). Despite intensive efforts all approaches have not been overtly successful (9), suggesting that we need to better understand the underlying biology of tumor cells and their environment as they respond to immunotherapy. Recent studies have elucidated epigenetic pathway regulation of GBM tumor expansion (10), suggesting that combined epigenetic pathway inhibition with immunotherapy may be feasible. In this review, we discuss current GBM clinical trials and how immune system interactions with epigenetic pathways and signaling nodes can be delineated to uncover potential combination therapies for this incurable disease.
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spelling doaj.art-59735820d6ca442eb1da83427d26f1ca2022-12-21T16:58:20ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2018-11-01810.3389/fonc.2018.00521423004Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma MultiformeChristopher Chin0Emma S. Lunking1Macarena de la Fuente2Macarena de la Fuente3Nagi G. Ayad4Department of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, Sylvester Comprehensive Cancer Center, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, Sylvester Comprehensive Cancer Center, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United StatesDepartment of Neurology, University of Miami, Miami, FL, United StatesSylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United StatesDepartment of Psychiatry and Behavioral Sciences, Center for Therapeutic Innovation, Sylvester Comprehensive Cancer Center, Miami Project to Cure Paralysis, University of Miami Miller School of Medicine, Miami, FL, United StatesGlioblastoma Multiforme (GBM) is the most common malignant primary brain tumor. Despite aggressive multimodality treatment it remains one of the most challenging and intractable cancers (1]. While current standard of care treatment for GBM is maximal safe surgical resection, systemic chemotherapy with Temozolimide (TMZ), and radiation therapy, the current prognosis of GBM patients remains poor, with a median overall survival of 12–15 months (2, 3). Therefore, other treatments are needed to provide better outcomes for GBM patients. Immunotherapy is one of the most promising new cancer treatment approaches. Immunotherapy drugs have obtained regulatory approval in a variety of cancers including melanoma (4), Hodgkin lymphoma (5), and non-small cell lung cancer (6). The basis of immunotherapy in cancer treatment is linked to stimulating the immune system to recognize cancer cells as foreign, thereby leading to the eventual elimination of the tumor. One form of immunotherapy utilizes vaccines that target tumor antigens (7), while other approaches utilize T-cells in patients to stimulate them to attack tumor cells (8). Despite intensive efforts all approaches have not been overtly successful (9), suggesting that we need to better understand the underlying biology of tumor cells and their environment as they respond to immunotherapy. Recent studies have elucidated epigenetic pathway regulation of GBM tumor expansion (10), suggesting that combined epigenetic pathway inhibition with immunotherapy may be feasible. In this review, we discuss current GBM clinical trials and how immune system interactions with epigenetic pathways and signaling nodes can be delineated to uncover potential combination therapies for this incurable disease.https://www.frontiersin.org/article/10.3389/fonc.2018.00521/fullglioblastomaimmunotherapeuticclinical trialepigeneticlong non coding RNA
spellingShingle Christopher Chin
Emma S. Lunking
Macarena de la Fuente
Macarena de la Fuente
Nagi G. Ayad
Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
Frontiers in Oncology
glioblastoma
immunotherapeutic
clinical trial
epigenetic
long non coding RNA
title Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
title_full Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
title_fullStr Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
title_full_unstemmed Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
title_short Immunotherapy and Epigenetic Pathway Modulation in Glioblastoma Multiforme
title_sort immunotherapy and epigenetic pathway modulation in glioblastoma multiforme
topic glioblastoma
immunotherapeutic
clinical trial
epigenetic
long non coding RNA
url https://www.frontiersin.org/article/10.3389/fonc.2018.00521/full
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AT macarenadelafuente immunotherapyandepigeneticpathwaymodulationinglioblastomamultiforme
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