Abstract
Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. GBM is very aggressive due to its poor cellular differentiation and invasiveness, which makes complete surgical resection virtually impossible. Therefore, GBMs invasive nature as well as its intrinsic resistance to current treatment modalities makes it a unique therapeutic challenge. Extensive examination of human GBM specimens has uncovered that these tumors overexpress a variety of receptors that are virtually absent in the surrounding non-neoplastic brain. Human GBMs overexpress receptors for cytokines, growth factors, ephrins, urokinase-type plasminogen activator (uPA), and transferrin, which can be targeted with high specificity by linking their ligands with highly cytotoxic molecules, such as Diptheria toxin and Pseudomonas exotoxin A. We review the preclinical development and clinical translation of targeted toxins for GBM. In view of the clinical experience, we conclude that although these are very promising therapeutic modalities for GBM patients, efforts should be focused on improving the delivery systems utilized in order to achieve better distribution of the immuno-toxins in the tumor/resection cavity. Delivery of targeted toxins using viral vectors would also benefit enormously from improved strategies for local delivery.
Keywords: IL-13, IL-13Rα2, TGF-α, EGFR, EGFRvIII, pseudomonas exotoxin, diphtheria toxin, gene therapy, targeted toxins
Anti-Cancer Agents in Medicinal Chemistry
Title: Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation
Volume: 11 Issue: 8
Author(s): Marianela Candolfi, Kurt M. Kroeger, Weidong Xiong, Chunyan Liu, Mariana Puntel, Kader Yagiz, AKM Ghulam Muhammad, Yohei Mineharu, David Foulad, Mia Wibowo, Hikmat Assi, Gregory J. Baker, Pedro R. Lowenstein and Maria G. Castro
Affiliation:
Keywords: IL-13, IL-13Rα2, TGF-α, EGFR, EGFRvIII, pseudomonas exotoxin, diphtheria toxin, gene therapy, targeted toxins
Abstract: Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. GBM is very aggressive due to its poor cellular differentiation and invasiveness, which makes complete surgical resection virtually impossible. Therefore, GBMs invasive nature as well as its intrinsic resistance to current treatment modalities makes it a unique therapeutic challenge. Extensive examination of human GBM specimens has uncovered that these tumors overexpress a variety of receptors that are virtually absent in the surrounding non-neoplastic brain. Human GBMs overexpress receptors for cytokines, growth factors, ephrins, urokinase-type plasminogen activator (uPA), and transferrin, which can be targeted with high specificity by linking their ligands with highly cytotoxic molecules, such as Diptheria toxin and Pseudomonas exotoxin A. We review the preclinical development and clinical translation of targeted toxins for GBM. In view of the clinical experience, we conclude that although these are very promising therapeutic modalities for GBM patients, efforts should be focused on improving the delivery systems utilized in order to achieve better distribution of the immuno-toxins in the tumor/resection cavity. Delivery of targeted toxins using viral vectors would also benefit enormously from improved strategies for local delivery.
Export Options
About this article
Cite this article as:
Candolfi Marianela, M. Kroeger Kurt, Xiong Weidong, Liu Chunyan, Puntel Mariana, Yagiz Kader, Ghulam Muhammad AKM, Mineharu Yohei, Foulad David, Wibowo Mia, Assi Hikmat, J. Baker Gregory, R. Lowenstein Pedro and G. Castro Maria, Targeted Toxins for Glioblastoma Multiforme: Pre-Clinical Studies and Clinical Implementation, Anti-Cancer Agents in Medicinal Chemistry 2011; 11 (8) . https://dx.doi.org/10.2174/187152011797378689
DOI https://dx.doi.org/10.2174/187152011797378689 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
The Relationship Between Lithium and Cancer Proliferation: A Case-Based Review of the Literature
Current Drug Metabolism Arylpyrazoles: Heterocyclic Scaffold of Immense Therapeutic Application
Current Organic Chemistry Dynamic Contrast Enhanced Magnetic Resonance Imaging in Oncology:Theory, Data Acquisition,Analysis, and Examples
Current Medical Imaging Repurposing Chloroquine Analogs as an Adjuvant Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Targeted Alpha Therapy with 213Bi
Current Radiopharmaceuticals Levetiracetam might act as an efficacious drug to attenuate cognitive deficits of Alzheimer’s disease
Current Topics in Medicinal Chemistry HLA-G and Inflammatory Diseases
Inflammation & Allergy - Drug Targets (Discontinued) Association of Posture Instability with Dopamine Drop of Nigrostriatal System and Hypometabolism of Cerebral Cortex in Parkinson’s Disease
Current Neurovascular Research Circular RNAs and Glioma: Small Molecule with Big Actions
Current Molecular Medicine Small Molecules with EGFR-TK Inhibitor Activity
Current Drug Targets Abnormal Choline Phospholipid Metabolism in Breast and Ovary Cancer:Molecular Bases for Noninvasive Imaging Approaches
Current Medical Imaging Nanomedicine and its Application in Treatment of Microglia-mediated Neuroinflammation
Current Medicinal Chemistry Pore-forming Peptides: A New Treatment Option for Cancer
Current Medicinal Chemistry CASC15: A Tumor-Associated Long Non-Coding RNA
Current Pharmaceutical Design Refractory Angina Pectoris: Lessons from the Past and Current Perspectives
Current Pharmaceutical Design Marine Drugs: A Hidden Wealth and a New Epoch for Cancer Management
Current Drug Metabolism A QSAR Study on Novel Series of Carbonic Anhydrase Inhibitors hCA IX—Tumor-Associated (Hypoxia)
Medicinal Chemistry Targeting Proteasomes with Naturally Occurring Compounds in Cancer Treatment
Current Cancer Drug Targets Peptide Targeted Copper-64 Radiopharmaceuticals
Current Topics in Medicinal Chemistry Graphical Abstracts:
Central Nervous System Agents in Medicinal Chemistry