Combination therapy to checkmate Glioblastoma: clinical challenges and advances

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Abstract

Combination therapy is increasingly becoming the cornerstone of current day antitumor therapy. Glioblastoma multiforme is an aggressive brain tumor with a dismal median survival post diagnosis and a high rate of disease recurrence. The poor prognosis can be attributed to unique treatment limitations, which include the infiltrative nature of tumor cells, failure of anti-glioma drugs to cross the blood–brain barrier, tumor heterogeneity and the highly metastatic and angiogenic nature of the tumor making cells resistant to chemotherapy. Combination therapy approach is being developed against glioblastoma with new innovative combination drug regimens being tested in preclinical and clinical trials. In this review, we discuss the pathophysiology of glioblastoma, diagnostic markers, therapeutic targeting strategies, current treatment limitations, novel combination therapies in the context of current treatment options and the ongoing clinical trials for glioblastoma therapy.

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Most cited references 92

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The blockade of immune checkpoints in cancer immunotherapy.

Drew M Pardoll (2012)

Among the most promising approaches to activating therapeutic antitumour immunity is the blockade of immune checkpoints. Immune checkpoints refer to a plethora of inhibitory pathways hardwired into the immune system that are crucial for maintaining self-tolerance and modulating the duration and amplitude of physiological immune responses in peripheral tissues in order to minimize collateral tissue damage. It is now clear that tumours co-opt certain immune-checkpoint pathways as a major mechanism of immune resistance, particularly against T cells that are specific for tumour antigens. Because many of the immune checkpoints are initiated by ligand-receptor interactions, they can be readily blocked by antibodies or modulated by recombinant forms of ligands or receptors. Cytotoxic T-lymphocyte-associated antigen 4 (CTLA4) antibodies were the first of this class of immunotherapeutics to achieve US Food and Drug Administration (FDA) approval. Preliminary clinical findings with blockers of additional immune-checkpoint proteins, such as programmed cell death protein 1 (PD1), indicate broad and diverse opportunities to enhance antitumour immunity with the potential to produce durable clinical responses.

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Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

Heidi Phillips, Samir Kharbanda, Ruihuan Chen … (2006)

Previously undescribed prognostic subclasses of high-grade astrocytoma are identified and discovered to resemble stages in neurogenesis. One tumor class displaying neuronal lineage markers shows longer survival, while two tumor classes enriched for neural stem cell markers display equally short survival. Poor prognosis subclasses exhibit markers either of proliferation or of angiogenesis and mesenchyme. Upon recurrence, tumors frequently shift toward the mesenchymal subclass. Chromosomal locations of genes distinguishing tumor subclass parallel DNA copy number differences between subclasses. Functional relevance of tumor subtype molecular signatures is suggested by the ability of cell line signatures to predict neurosphere growth. A robust two-gene prognostic model utilizing PTEN and DLL3 expression suggests that Akt and Notch signaling are hallmarks of poor prognosis versus better prognosis gliomas, respectively.

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A restricted cell population propagates glioblastoma growth following chemotherapy

Jian Chen, Yanjiao Li, Tzong-Shiue Yu … (2012)

Glioblastoma multiforme (GBM) is the most common primary malignant brain tumor, with a median survival of about one year 1 . This poor prognosis is due to therapeutic resistance and tumor recurrence following surgical removal. Precisely how recurrence occurs is unknown. Using a genetically-engineered mouse model of glioma, we identify a subset of endogenous tumor cells that are the source of new tumor cells after the drug, temozolomide (TMZ), is administered to transiently arrest tumor growth. A Nestin-ΔTK-IRES-GFP (Nes-ΔTK-GFP) transgene that labels quiescent subventricular zone adult neural stem cells also labels a subset of endogenous glioma tumor cells. Upon arrest of tumor cell proliferation with TMZ, pulse-chase experiments demonstrate a tumor re-growth cell hierarchy originating with the Nes-ΔTK-GFP transgene subpopulation. Ablation of the GFP+ cells with chronic ganciclovir administration significantly arrested tumor growth and combined TMZ-ganciclovir treatment impeded tumor development. These data indicate the existence of a relatively quiescent subset of endogenous glioma cells that are responsible for sustaining long-term tumor growth through the production of transient populations of highly proliferative cells.

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Author and article information

Contributors

Saikat Nandi: snandi@cshl.edu

Sonali Bhattacharjee:

ORCID: http://orcid.org/0000-0003-0522-3361

bhattacharjee@cshl.edu

Journal

Journal ID (nlm-ta): Clin Transl Med

Journal ID (iso-abbrev): Clin Transl Med

Title: Clinical and Translational Medicine

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Electronic): 2001-1326

Publication date (Electronic): 16 October 2018

Publication date PMC-release: 16 October 2018

Publication date Collection: 2018

Volume: 7

Electronic Location Identifier: 33

Affiliations

ISNI 0000 0004 0387 3667, GRID grid.225279.9, Cold Spring Harbor Laboratory, ; Cold Spring Harbor, NY USA

Author information

Sonali Bhattacharjee http://orcid.org/0000-0003-0522-3361

Article

Publisher ID: 211

DOI: 10.1186/s40169-018-0211-8

PMC ID: 6191404

PubMed ID: 30327965

SO-VID: efbb1109-e671-4a99-b0a0-bb9fdb6f4599

License:

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.

History

Date received : 6 August 2018

Date accepted : 1 October 2018

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ScienceOpen disciplines: Medicine

Keywords: combination therapy,glioblastoma multiforme,glioblastoma stem cells,targeted cancer therapy,tumor microenvironment,precision medicine,chemotherapy,tumor heterogeneity,drug resistance,radiotherapy,immunotherapy,clinical trials

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ScienceOpen disciplines: Medicine

Keywords: combination therapy, glioblastoma multiforme, glioblastoma stem cells, targeted cancer therapy, tumor microenvironment, precision medicine, chemotherapy, tumor heterogeneity, drug resistance, radiotherapy, immunotherapy, clinical trials

Combination therapy to checkmate Glioblastoma: clinical challenges and advances

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Most cited references 92

The blockade of immune checkpoints in cancer immunotherapy.

Molecular subclasses of high-grade glioma predict prognosis, delineate a pattern of disease progression, and resemble stages in neurogenesis.

A restricted cell population propagates glioblastoma growth following chemotherapy

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