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
-
Recombinant Immunotoxins for the Treatment of Chemoresistant Hematologic Malignancies
Current Pharmaceutical Design P53 Gene Therapy Sensitizes Resistant Breast Cancer Cells to Doxorubicin Chemotherapy
Drug Delivery Letters Antidepressant Desipramine Leads to C6 Glioma Cell Autophagy: Implication for the Adjuvant Therapy of Cancer
Anti-Cancer Agents in Medicinal Chemistry Immunophilin Dysfunction and Neuropathology
Current Medicinal Chemistry Fibroblast Growth Factor-2 Antagonist and Antiangiogenic Activity of Long-Pentraxin 3-Derived Synthetic Peptides
Current Pharmaceutical Design Using Nutrigenomics to Evaluate Apoptosis as a Preemptive Target in Cancer Prevention
Current Cancer Drug Targets Tyrosine Kinase Update: Role and Response in Cancer Therapy
Current Cancer Therapy Reviews Oligonucleotide Aptamers for Glioma Targeting: An Update
Central Nervous System Agents in Medicinal Chemistry HSV-1 Viral Oncolysis and Molecular Imaging with PET
Current Cancer Drug Targets The Emerging Role of Poly(ADP-Ribose) Polymerase Inhibitors in Cancer Treatment
Current Drug Targets Neural Differentiation and Therapeutic Potential of Adipose Tissue Derived Stem Cells
Current Stem Cell Research & Therapy Intersection of MicroRNA and Gene Regulatory Networks and their Implication in Cancer
Current Pharmaceutical Biotechnology Is the Clinical Use of Cannabis by Oncology Patients Advisable?
Current Medicinal Chemistry Plasminogen Receptors in Human Malignancies: Effects on Prognosis and Feasibility as Targets for Drug Development
Current Drug Targets Importance of Aquaporins in the Physiopathology of Brain Edema
Current Pharmaceutical Design Inhibition of Autophagy Strengthens Celastrol-Induced Apoptosis in Human Pancreatic Cancer In Vitro and In Vivo Models
Current Molecular Medicine Soft Matter Assemblies as Nanomedicine Platforms for Cancer Chemotherapy: A Journey from Market Products Towards Novel Approaches
Current Topics in Medicinal Chemistry Nanocarriers Conjugated with Cell Penetrating Peptides: New Trojan Horses by Modern Ulysses
Current Pharmaceutical Biotechnology The Current State of Potential Therapeutic Modalities for Glioblastoma Multiforme: A Clinical Review
Current Drug Metabolism B7-H3-targeted Radioimmunotherapy of Human Cancer
Current Medicinal Chemistry