Abstract
Malignant gliomas are the most common and the deadliest brain malignancies in adults. Despite the lack of a complete understanding of the biology of these tumors, significant advances have been made in the past decades. One of the key discoveries made in the area of malignant gliomas is that these tumors can be induced and maintained by aberrant signaling networks. In this context, the Ras pathway has been extensively exploited, from both basic and translational perspectives. Although somatic oncogenic mutations of Ras genes are frequent in several cancer types, early investigations on gliomas revealed disappointing facts that the Ras mutations are nearly absent in malignant gliomas and that the BRAF mutations are present in a very small percentage of gliomas. Therefore, the observed deregulation of the Ras-RAF-ERK signaling pathway in gliomas is attributed to its upstream positive regulators, including, EGFR and PDGFR known to be highly active in the majority of malignant gliomas. In contrast to the initial negative results on the somatic mutations of H-Ras, K-Ras and BRAF, recent breakthrough studies on pediatric low-grade astrocytomas uncovered genetic alterations of the BRAF gene involving copy number gains and rearrangements. The 7q34 rearrangements result in a novel in-frame KIAA1549:BRAF fusion gene that possesses constitutive BRAF kinase activity resembling oncogenic BRAF (V600E). In light of the earlier findings and recent breakthroughs, this review summarizes our current understanding of the Ras-RAF-ERK signaling pathway in gliomas and the outcome of preclinical and clinical studies that evaluated the efficacy of Ras-targeted therapy in malignant gliomas.
Keywords: Akt, Avastin, BRAF, chemotherapy, EGFR, glioma, PDGFR, RAF, Ras.
Current Cancer Drug Targets
Title:Targeting Ras-RAF-ERK and its Interactive Pathways as a Novel Therapy for Malignant Gliomas
Volume: 10 Issue: 8
Author(s): H.-W. Lo
Affiliation:
Keywords: Akt, Avastin, BRAF, chemotherapy, EGFR, glioma, PDGFR, RAF, Ras.
Abstract: Malignant gliomas are the most common and the deadliest brain malignancies in adults. Despite the lack of a complete understanding of the biology of these tumors, significant advances have been made in the past decades. One of the key discoveries made in the area of malignant gliomas is that these tumors can be induced and maintained by aberrant signaling networks. In this context, the Ras pathway has been extensively exploited, from both basic and translational perspectives. Although somatic oncogenic mutations of Ras genes are frequent in several cancer types, early investigations on gliomas revealed disappointing facts that the Ras mutations are nearly absent in malignant gliomas and that the BRAF mutations are present in a very small percentage of gliomas. Therefore, the observed deregulation of the Ras-RAF-ERK signaling pathway in gliomas is attributed to its upstream positive regulators, including, EGFR and PDGFR known to be highly active in the majority of malignant gliomas. In contrast to the initial negative results on the somatic mutations of H-Ras, K-Ras and BRAF, recent breakthrough studies on pediatric low-grade astrocytomas uncovered genetic alterations of the BRAF gene involving copy number gains and rearrangements. The 7q34 rearrangements result in a novel in-frame KIAA1549:BRAF fusion gene that possesses constitutive BRAF kinase activity resembling oncogenic BRAF (V600E). In light of the earlier findings and recent breakthroughs, this review summarizes our current understanding of the Ras-RAF-ERK signaling pathway in gliomas and the outcome of preclinical and clinical studies that evaluated the efficacy of Ras-targeted therapy in malignant gliomas.
Export Options
About this article
Cite this article as:
Lo H.-W., Targeting Ras-RAF-ERK and its Interactive Pathways as a Novel Therapy for Malignant Gliomas, Current Cancer Drug Targets 2010; 10 (8) . https://dx.doi.org/10.2174/156800910793357970
DOI https://dx.doi.org/10.2174/156800910793357970 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
Recent Development in Fluorescent Probes for Copper Ion Detection
Current Topics in Medicinal Chemistry Antitumor Activity and Structure-Activity Relationship of Diterpenoids with a Dehydroabietyl Skeleton
Combinatorial Chemistry & High Throughput Screening Gallium-68: A New Trend in PET Radiopharmacy
Current Radiopharmaceuticals Oncologic Imaging End-Points for the Assessment of Therapy Response
Recent Patents on Anti-Cancer Drug Discovery The Antitumor Efficiency of Zinc Finger Nuclease Combined with Cisplatin and Trichostatin A in Cervical Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry The Therapeutic Potential of Melatonin in Neurological Disorders
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery In Vitro Modeling of the Blood-Brain Barrier: Simplicity Versus Complexity
Current Pharmaceutical Design Recent Advances in Delivery Through the Blood-Brain Barrier
Current Topics in Medicinal Chemistry CD248: Reviewing its Role in Health and Disease
Current Drug Targets Rate Limiting Steps of AAV Transduction and Implications for Human Gene Therapy
Current Gene Therapy Long Non-coding RNA AFAP1-AS1 Facilitates Prostate Cancer Progression by Regulating miR-15b/IGF1R Axis
Current Pharmaceutical Design Brain Tumor Detection Using Machine Learning and Deep Learning: A Review
Current Medical Imaging Methylenetetrahydrofolate Reductase (MTHFR): A Novel Target for Cancer Therapy
Current Pharmaceutical Design Liposome-Encapsulated Photosensitizers Against Bacteria
Recent Patents on Anti-Infective Drug Discovery NK Cell Receptor and MHC Gene Polymorphisms, Potential Relevance in Malignancies
Current Cancer Therapy Reviews Targeting the Atypical Chemokine Receptor ACKR3/CXCR7: Phase 1 - Phage Display Peptide Identification and Characterization
Current Topics in Medicinal Chemistry Dietary Prevention of Cancer: Anticancer and Antiangiogenic Properties of Green Tea Polyphenols
Medicinal Chemistry Reviews - Online (Discontinued) Radiopharmaceutical Chemistry with Iodine-124: A Non-Standard Radiohalogen for Positron Emission Tomography
Medicinal Chemistry Iron Oxide Nanoparticles Synthesized Via Green Tea Extract for Doxorubicin Delivery
Current Nanoscience Notch Signalling Pathways and Their Importance in the Treatment of Cancers
Current Drug Targets