Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies

1st Edition, Volume 15 - June 25, 2021
Imprint: Academic Press
Editors: Ramasamy Paulmurugan, Tarik F. Massoud
Language: English
Hardback ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 5 6 7 - 8
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 1 5 6 8 - 5

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies brings current knowledge from an international team of experts on the science a… Read more

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Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies brings current knowledge from an international team of experts on the science and clinical management of glioblastoma chemoresistance. The book discusses topics such as molecular mechanisms of chemoresistance, experimental models to study chemoresistance, chemoresistance to drugs other than Temozolomide, and specific strategies to reverse chemoresistance. Additionally, it encompasses information on how to mitigate chemoresistance by targeted enhancement of p53 function. This book is a valuable resource for cancer researchers, oncologists, neuro-oncologists and other members of the biomedical field.

Glioblastoma (GBM) is the most invasive and malignant primary brain tumor in humans with poor survival after diagnosis, therefore it is imperative that molecular and cellular mechanisms behind therapy resistant GBM cells, as well as the therapeutic strategies available to counter the resistance are comprehensively understood.

Cover image
Title page
Table of Contents
Copyright
Cover Image Legend
Aims and Scope for Series “Cancer Sensitizing Agents for Chemotherapy”
About the Series Editor
Aims and Scope of the Volume
About the Volume Editors
Preface
Contributors
Chapter 1: Overview of glioblastoma biological hallmarks and molecular pathology
Abstract
Conflict of interest
Introduction
Biological hallmarks
Molecular pathology
Molecular markers
Epigenetic markers
Conclusions and future perspectives
Chapter 2: Past and present drug treatments for glioblastoma
Abstract
Conflict of interest
Introduction
Brief history of glioblastoma
Chemotherapy
Tyrosine kinase pathway
Immunotherapy
Conclusion
Chapter 3: Investigational new drugs against glioblastoma
Abstract
Acknowledgments
Conflict of interest
Introduction
Agents that target DNA integrity
Agents that target epigenetic determinants of chromosome structure and gene transcription
Agents that directly alter cell cycle or cell death regulation
Agents that directly alter protein homeostasis
Targeting upstream molecular pathways
Synthetic lethality and drug delivery
Conclusions
Chapter 4: Molecular mechanisms in temozolomide-resistant glioblastoma
Abstract
Acknowledgment
Conflict of interest
Introduction
Molecular events in GBM cells after TMZ treatment
Molecular events in TMZ-resistant GBM cells after TMZ treatment
Therapeutic approaches
Methods for identification of novel targets for sensitizing TMZ
Conclusions and future directions
Chapter 5: Glioma stem cells and associated molecular mechanisms in Glioblastoma Chemoresistance
Abstract
Conflict of interest
Introduction
Current therapies and the role of GSCs
Glioma stem-like cell biology aiding survival
Specific molecular pathways of GSC resistance to chemotherapy
Conclusion
Chapter 6: Signaling in the tumor microenvironment of therapy-resistant glioblastoma
Abstract
Conflict of interest
Introduction
TME
Signals from the ECM
Tumor/stroma interactions
Phospholipase C (PLC/PKC)
Effects of therapy on the TME
Targeting the TME
Conclusion
Chapter 7: Intratumoral heterogeneity associated with glioblastoma drug response and resistance
Abstract
Conflict of interest
Introduction
Genetic and transcriptomic ITH
Cellular and functional ITH
Molecular mechanisms of treatment resistance
Cell-intrinsic and -extrinsic mechanisms of resistance
Conclusions
Chapter 8: Role of apoptosis, autophagy, and the unfolded protein response in glioblastoma chemoresistance
Abstract
Conflict of interest
Introduction
Apoptosis
P53
Apoptosis and chemoresistance
Chemoresistance in glioblastoma
Autophagy pathway
The dual roles of autophagy in glioblastoma promotion and suppression
Endoplasmic reticulum stress, and unfolded protein response (UPR)
Cross talk between UPR, autophagy, and apoptosis
Role of UPR in glioblastoma chemoresistance
Role of UPR branches in GBM-induced chemoresistant to TMZ
UPR affects chemotherapy-induced cell death in GBM
How simvastatin/TMZ affect GBM chemoresistance
Tissue-engineered tumor models
Bioengineered glioblastoma and neuroblastoma in vitro models
Brain tumor tissue-engineered models for chemotherapeutic evaluations
Conclusion
Chapter 9: Role of multidrug resistance in glioblastoma chemoresistance_ Focus on ABC transporters
Abstract
Acknowledgments
Authors’ contributions
Conflict of interest
Introduction
Structure and functions of ABC proteins
ABC transporters in glioblastoma
Clinical value
Conclusion
Chapter 10: Role of mitochondrial reactive oxygen species in glioblastoma drug resistance and strategies for therapeutic intervention
Abstract
Acknowledgments
Conflict of interest
Introduction
Reactive oxygen species in GBM
Conclusions
Chapter 11: Glioblastoma cell-induced immunosuppression causing chemoresistance
Abstract
Conflict of interest
Introduction
The glioblastoma secretome
Cytokine-induced immunosuppression in glioblastoma
Indoleamine 2,3-dioxygenase and the kynurenine pathway
Programmed death-ligand 1 (PD-L1) (cluster of differentiation, CD 274)
Chapter 12: Role of cell quiescence in glioblastoma cytotoxic resistance and strategies for therapeutic intervention
Abstract
Acknowledgments
Conflict of interest
Introduction
Cell quiescence
Quiescence and treatment resistance
Molecular drivers of quiescence
Targeting quiescent GBM tumor cells
Methods to identify and isolate quiescent cells
Vital dye retention, proliferative potential, and cytotoxic sensitivity in glioblastoma cells
Conclusions
Chapter 13: The molecular and cellular effects of radiotherapy-induced microenvironment changes on potential chemoresistance in glioblastoma
Abstract
Conflict of interest
Introduction
Extracellular microenvironment of the brain in glioblastoma
Radiation-induced changes in the brain and GBM microenvironment
Therapeutic implications and future directions
Conclusions
Chapter 14: Molecular and cellular mechanisms in recurrent glioblastoma chemoresistance
Abstract
Acknowledgment
Conflict of interest
Introduction
Recurrent glioblastoma
Glioblastoma stem cells
Other intrinsic and extrinsic mechanisms involved in the recurrence of GBM
Conclusion
Chapter 15: Role of long noncoding RNAs in temozolomide-resistant glioblastoma
Abstract
Acknowledgments
Conflict of interest
Introduction
GBM cancer
Long noncoding RNA
Cancer susceptibility candidate 2
Key cellular components in therapy resistance
Long noncoding RNA (lncRNA)-mediated gene silencing through polycomb mechanisms
Noncoding RNA epigenetics
lncRNA classification
Functions of LncRNA in the nucleus
Functions of LncRNAs in regulating gene expression in the cytoplasm
Mechanisms of actions of lncRNA
LncRNA classification based on region implicated by the lncRNA
Conclusions
Chapter 16: Mechanisms of glioblastoma resistance to antiangiogenic agents and reversal approaches
Abstract
Conflict of interest
Introduction
Tumor neovascularization through angiogenesis, vasculogenesis, and vascular mimicry
Antiangiogenic therapies and development of resistance
Mechanisms of AAT resistance and possible intervention
Chapter 17: Treatment and resistance of glioblastoma to CAR T-cell immunotherapies
Abstract
Conflict of interest
Introduction to CAR T-cell therapy
CAR T-cell therapy in GBM: Recent clinical advances
Challenges and mechanisms of resistance to CAR T-cell therapy in GBM
Future directions to overcome resistance
Conclusions
Chapter 18: On-chip analysis of glioblastoma cell chemoresistance
Abstract
Acknowledgments
Funding
Competing interests
Conflict of interest
Introduction
Exosomal RNA analysis for monitoring chemoresistance in GBM
Outlook
Chapter 19: Three-dimensional in vitro models to study potentiation of glioblastoma resistance by hypoxia
Abstract
Conflict of interest
Introduction
Hypoxia as a tumor microenvironment component in glioblastoma
In vitro 3D model for glioblastoma
Conclusion
Chapter 20: Chemoresistance mechanisms in mouse models of glioblastoma
Abstract
Acknowledgment
Conflict of interest
Introduction
Factors involved in GBM chemoresistance
Mouse models
Conclusion
Chapter 21: Therapeutic approaches to overcome temozolomide resistance in glioblastoma
Abstract
Conflict of interest
Introduction
Targeting DNA repair mechanisms
Targeting receptor tyrosine kinases and cellular pathways
Antiangiogenic therapies
Targeting cancer stem cells
Tumor treating fields
Alternative delivery methods
Conclusion
Chapter 22: Understanding signal transduction pathways to overcome targeted therapy resistance in glioblastoma
Abstract
Conflict of interest
Introduction
Current status of chemotherapy in GBM treatment
Molecular mechanisms of TMZ resistance in GBM cells
Chemoresistance of GBM induced by plasma membrane-localizing receptor-mediated survival signaling
Chemoresistance of GBM induced by Hippo/Yes associated-protein 1 (YAP)- mediated survival signaling
Chemoresistance of GBMs induced by p16INK4a/p14ARF-mediated survival signaling
Chemoresistance induced by cancer stem-like cells, TME, heterogeneity, and plasticity in GBMs
miRNA-mediated chemoresistance
Conclusions and perspectives
Chapter 23: Targeting the molecular mechanisms of glioma stem cell resistance to chemotherapy
Abstract
Conflict of interest
Introduction
The adaptive microenvironment of glioma stem cells
Mechanisms of glioma stem cell resistance to chemotherapy
Therapeutic strategies to overcome glioma stem cell resistance to chemotherapy
Conclusion
Chapter 24: Immunotherapy for glioblastoma as a means to overcome resistance to standard therapy
Abstract
Conflict of interest
Introduction: Evolution of therapy for glioblastoma
Immune surveillance and immunotherapy strategies in translation
Lymphatic drainage in the CNS to secondary lymphoid organs
Overcoming limited migration of DC therapies
Immune checkpoint inhibitors in glioma
Mechanisms of chemotherapy resistance and implications for immune activation
Conclusion
Chapter 25: Role of microRNA therapy in presensitizing glioblastoma cells to temozolomide treatment
Abstract
Conflict of interest
Introduction
Role of microRNAs in cells
Regulatory role of miRNAs in cancer
Regulatory role of microRNAs in GBM biology
MiRNAs role in therapeutic sensitization of GBM to chemotherapy
The role of miRNAs in therapeutic sensitization of GBM to TMZ
MiRNAs targeting GSCs to achieve GBM therapy
MicroRNAs targeting multiple cellular mechanisms as potential future therapies for GBM
Conclusion and future perspectives
Chapter 26: Drug penetration through the blood–brain barrier after radiotherapy: New approaches to bypass glioblastoma chemoresistance
Abstract
Acknowledgment
Conflict of interest
Introduction
The molecular mechanisms and genetics of chemoresistance in glioblastoma
Alterations in the BBB permeability to increase the action of doxorubicin
Consolidated and new treatments for glioblastoma
Ionizing radiation interferes with BBB permeability by facilitating the passage of drugs
Conclusion
Chapter 27: Nanoparticles beyond the blood-brain barrier for glioblastoma
Abstract
Conflict of interest
Introduction
Barriers to delivery
Emerging delivery strategies to mitigate the BBB
Conclusion
Chapter 28: Small molecules targeting misfolded mutants of p53 as a rescue strategy to improve glioblastoma chemotherapy
Abstract
Conflict of interest
Introduction
History of the tumor suppressor p53
p53 regulation
p53 structure
The p53 pathway
p53 mutants
Distribution and frequency of p53 mutations and their clinical relevance
p53 with single allele, both allele and null mutants
Therapeutic strategies targeting p53
Therapeutic approaches to restore wild-type p53 function of mutant p53 protein via restoration of structural stability
Considerations and principles of drugs that rescue mutant p53 structure
Assay systems to identify new drugs stabilizing p53 protein structure
Drugs that rescue the deleterious effect of p53 structural mutations (Tables 1 and 2)
Limitations of compounds targeting structural mutations of p53
Synergizing the effect of drugs targeting mutant p53
Conclusion
Chapter 29: p53 supplementation as a targeted cancer gene therapy for glioblastoma
Abstract
Conflict of interest
Role of p53 in cell cycle regulation
TP53 mutation and its relevance to glioblastoma development
Correlation of TP53 status to grades of gliomas
TP53-based therapeutic strategies for glioblastoma
p53-targeted cancer gene therapy
Clinical status of p53 cancer gene therapy
Future perspectives and therapeutic potentials
Index

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Health

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies

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Tarik F. Massoud

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