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Glioblastoma, Part II: Molecular Targets and Clinical Trials
NEUROSURGERY CLINICS OF NORTH AMERICA (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Linda M. Liau Source Type: research

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ELSEVIER (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Contributors
DANIEL K. RESNICK, MD, MS (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Contents
Linda M. Liau (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Neurosurgery Clinics of North America
Current State of the Art in Spinal Cord Injury (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Source Type: research

Glioblastoma: Molecular Mechanisms and Clinical Trials
Despite growing basic research on the molecular genetics and mechanisms of brain tumor biology and new clinical trials for brain tumors, glioblastoma has remained a formidable foe. In this issue of Neurosurgery Clinics of North America, an authoritative panel of researchers and clinicians critically reviews the current state-of-the-field to provide a comprehensive guide to modern molecular considerations and clinical trials for glioblastoma, with hopes of enhancing future research in this area. The contributors detail many of the key laboratory experiments and clinical protocols that are currently being investigated, integ...
Source: Neurosurgery Clinics of North America - March 27, 2021 Category: Neurosurgery Authors: Linda M. Liau Tags: Preface Source Type: research

Pediatric Gliomas
Next-generation sequencing of pediatric gliomas has revealed the importance of molecular genetic characterization in understanding the biology underlying these tumors and a breadth of potential therapeutic targets. Promising targeted therapies include mTOR inhibitors for subependymal giant cell astrocytomas in tuberous sclerosis, BRAF and MEK inhibitors mainly for low-grade gliomas, and MEK inhibitors for NF1-deficient BRAF:KIAA fusion tumors. Challenges in developing targeted molecular therapies include significant intratumoral and intertumoral heterogeneity, highly varied mechanisms of treatment resistance and immune esc...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Sophie M. Peeters, Yagmur Muftuoglu, Brian Na, David J. Daniels, Anthony C. Wang Source Type: research

Molecularly Targeted Clinical Trials
Glioblastoma remains incurable despite advances in surgery, radiation, and chemotherapy, underscoring the need for new therapies. The genetic heterogenicity, presence of redundant molecular pathways, and the blood-brain barrier have limited the applicability of molecularly targeted agents. The therapeutic benefit seen with a small subset of patients suggests, however, that patient selection is critical. Recent investigations show that molecularly targeted synthetic lethality is a promising complementary approach. The article provides an overview of the challenges of molecularly targeted therapy in adults with glioblastoma,...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Matthew A. Smith-Cohn, Orieta Celiku, Mark R. Gilbert Source Type: research

Therapeutic Delivery to Central Nervous System
Therapies for glioblastoma face several physiologic hurdles. The blood-brain barrier (BBB) and blood-brain-tumor barrier (BTB) present impediments to therapeutic delivery of drugs to the central nervous system. Strategies to disrupt or bypass the native BBB are necessary to deliver therapeutic agents. Techniques to bypass the BBB/BTB include implantable controlled-release polymer systems, intracavitary drug delivery, direct injection of viral vectors, and infusion via convection-enhanced delivery. Ideal methods and agents to accomplish the goal providing survival benefit are yet to be determined. Further development of met...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Katherine E. Kunigelis, Michael A. Vogelbaum Source Type: research

CAR T Cells
Chimeric antigen receptor T (CAR-T) cells, an immunotherapy that demonstrates marked success in treatment of hematologic malignancies, are an emergent therapeutic for patients with glioblastoma (GBM). GBM CAR-T trials have focused on targeting well-characterized antigens in the pathogenesis of GBM. Early stage trials demonstrate initial success in terms of safety and tolerability. There is preliminary evidence of antitumor activity and localization of the CAR-T product to tumoral sites. There are mixed results regarding patient outcomes. Ongoing GBM CAR-T trials will target novel antigens, explore CAR-T combination therapy...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Thilan Tudor, Zev A. Binder, Donald M. O ’Rourke Source Type: research

Immunovirotherapy for the Treatment of Glioblastoma and Other Malignant Gliomas
Glioblastoma multiforme (GBM) represents one of the most challenging malignancies due to many factors including invasiveness, heterogeneity, and an immunosuppressive microenvironment. Current treatment modalities have resulted in only modest effect on outcomes. The development of viral vectors for oncolytic immunovirotherapy and targeted drug delivery represents a promising therapeutic prospect for GBM and other brain tumors. A host of genetically engineered viruses, herpes simplex virus, poliovirus, measles, and others, have been described and are at various stages of clinical development. Herein we provide a review of th...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Dagoberto Estevez-Ordonez, Gustavo Chagoya, Arsalaan Salehani, Travis J. Atchley, Nicholas M.B. Laskay, Matthew S. Parr, Galal A. Elsayed, Anil K. Mahavadi, Sage P. Rahm, Gregory K. Friedman, James M. Markert Source Type: research

The Role of Mismatch Repair in Glioblastoma Multiforme Treatment Response and Resistance
Mismatch repair (MMR) is a highly conserved DNA repair pathway that is critical for the maintenance of genomic integrity. This pathway targets base substitution and insertion-deletion mismatches, which primarily arise from replication errors that escape DNA polymerase proof-reading function. Here, the authors review key concepts in the molecular mechanisms of MMR in response to alkylation damage, approaches to detect MMR status in the clinic, and the clinical relevance of this pathway in glioblastoma multiforme treatment response and resistance. (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Nalin Leelatian, Christopher S. Hong, Ranjit S. Bindra Source Type: research

Targeting Glioma Stem Cells
Only a small fraction of the tumor cell population, glioma-initiating cells (GICs) help glioblastoma propagate, invade, evade immune recognition, repair DNA in response to radiation more efficiently, remodel the microenvironment for optimal growth, and actively pump out chemotherapies. Recent data hint that efforts toward GIC characterization and quantification can help predict patient outcomes, and yet the different subpopulations of GICs remain incompletely understood. A better understanding of GIC subtypes and functions proves critical for engineering targeted therapies. Challenges for doing so are discussed, and dopami...
Source: Neurosurgery Clinics of North America - February 18, 2021 Category: Neurosurgery Authors: Yagmur Muftuoglu, Frank Pajonk Source Type: research

Glioblastoma, Part I: Surgical Management and Adjuncts
NEUROSURGERY CLINICS OF NORTH AMERICA (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - November 20, 2020 Category: Neurosurgery Authors: Michael A. Vogelbaum Source Type: research

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ELSEVIER (Source: Neurosurgery Clinics of North America)
Source: Neurosurgery Clinics of North America - November 20, 2020 Category: Neurosurgery Source Type: research