Abstract
This article focuses on the possible application of antagonists of the G-protein coupled chemokine receptor, CXCR4, for the treatment of glioblastoma and summarises the evidence for CXCR4 antagonism being a viable therapeutic approach. Particular attention is paid to the role of this receptor in cancer stem cell biology, and the maintenance of CXCR4 expression by the glioblastoma key driver mutations. The expression of the CXCR4 receptor, and of its ligand stromal derived factor 1 (SDF-1, CXCL12), is maintained by intracellular pathways via positive feedback loops, and is associated with the epithelial mesenchymal transition (EMT) and the generation and self-renewal of cancer stem cells. SDF-1 and CXCR4 also play a role in the generation and maintenance of the perivascular stem cell niche which contains these cancer stem cells. The available data suggest that most, if not all, glioblastoma cancer stem cells rely on CXCR4 mediated signalling to maintain their phenotype. SDF-1 and CXCR4 are alsoinvolved in many other aspects of brain tumour biology including resistance to radio- and chemotherapy, the migration of cancer cells through the brain, the generation of the tumour blood supply and the recruitment of vascular progenitor cells. These properties suggest that a CXCR4 antagonist would help in the control of this disease.
Keywords: Cancer stem cell, CXCL12, CXCR4, EMT, glioblastoma, SDF-1, signaling.
Anti-Cancer Agents in Medicinal Chemistry
Title:CXCR4 and Glioblastoma
Volume: 16 Issue: 1
Author(s): Peter J. Richardson
Affiliation:
Keywords: Cancer stem cell, CXCL12, CXCR4, EMT, glioblastoma, SDF-1, signaling.
Abstract: This article focuses on the possible application of antagonists of the G-protein coupled chemokine receptor, CXCR4, for the treatment of glioblastoma and summarises the evidence for CXCR4 antagonism being a viable therapeutic approach. Particular attention is paid to the role of this receptor in cancer stem cell biology, and the maintenance of CXCR4 expression by the glioblastoma key driver mutations. The expression of the CXCR4 receptor, and of its ligand stromal derived factor 1 (SDF-1, CXCL12), is maintained by intracellular pathways via positive feedback loops, and is associated with the epithelial mesenchymal transition (EMT) and the generation and self-renewal of cancer stem cells. SDF-1 and CXCR4 also play a role in the generation and maintenance of the perivascular stem cell niche which contains these cancer stem cells. The available data suggest that most, if not all, glioblastoma cancer stem cells rely on CXCR4 mediated signalling to maintain their phenotype. SDF-1 and CXCR4 are alsoinvolved in many other aspects of brain tumour biology including resistance to radio- and chemotherapy, the migration of cancer cells through the brain, the generation of the tumour blood supply and the recruitment of vascular progenitor cells. These properties suggest that a CXCR4 antagonist would help in the control of this disease.
Export Options
About this article
Cite this article as:
Richardson J. Peter, CXCR4 and Glioblastoma, Anti-Cancer Agents in Medicinal Chemistry 2016; 16 (1) . https://dx.doi.org/10.2174/1871520615666150824153032
DOI https://dx.doi.org/10.2174/1871520615666150824153032 |
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
-
An Update on the Systemic Therapy of Malignant Salivary Gland Cancers: Role of Chemotherapy and Molecular Targeted Agents
Current Medicinal Chemistry - Anti-Cancer Agents Protein Tyrosine Phosphatases, New Targets for Cancer Therapy
Current Cancer Drug Targets Hematological Targets of Radiation Damage
Current Drug Targets CYP2A5 Induction and Hepatocellular Stress: An Adaptive Response to Perturbations of Heme Homeostasis
Current Drug Metabolism The Protein-Protein Interaction-Mediated Inactivation of PTEN
Current Molecular Medicine Phytochemical and Biological Activities of an Anticancer Plant Medicine: Brucea javanica
Anti-Cancer Agents in Medicinal Chemistry Blood-Brain Barrier Penetration and Drug Development from an Industrial Point of View
Current Medicinal Chemistry - Central Nervous System Agents Gefitinib Targets EGFR Dimerization and ERK1/2 Phosphorylation to Inhibit Pleural Mesothelioma Cell Proliferation
Current Cancer Drug Targets A Prooxidant Mechanism for the Anticancer and Chemopreventive Properties of Plant Polyphenols
Current Drug Targets Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer
Current Genomics A Review of Diabetes Mellitus and Exposure to the Environmental Toxicant Cadmium with an Emphasis on Likely Mechanisms of Action
Current Diabetes Reviews The State of the Problem of Achieving Extremely Low LDL Levels
Current Pharmaceutical Design Tissue-Specific Methylation of Long Interspersed Nucleotide Element-1 of Homo Sapiens (L1Hs) During Human Embryogenesis and Roles in Neural Tube Defects
Current Molecular Medicine Insights on the Use of Nanocarriers for Acne Alleviation
Current Drug Delivery Targeting Gene Therapy for Prostate Cancer
Current Pharmaceutical Design NF-κB Links Keratinocytes and Lymphocytes in the Pathogenesis of Psoriasis
Recent Patents on Inflammation & Allergy Drug Discovery Application of Pharmacogenomics to Dietary Cancer Chemoprevention
Current Pharmacogenomics Fish and Apoptosis: Studies in Disease and Pharmaceutical Design
Current Pharmaceutical Design 3-(4-Geranyloxy-3-Methoxyphenyl)-2-trans Propenoic Acid: A Novel Promising Cancer Chemopreventive Agent
Anti-Cancer Agents in Medicinal Chemistry Editorial:Tubulin-targeted Cancer Chemotherapeutics: Advances and Challenges
Current Topics in Medicinal Chemistry