Abstract
The inhibition of oncogenic signaling pathways has gained great interest for cancer therapy. In this context, the molecular chaperone heat shock protein 90 (HSP90) has emerged as a promising molecular target, since it is critically involved in maintaining stability, integrity and functions of key oncogenic proteins. A variety of HSP90 inhibitors have been developed in the past decade and have shown convincing anti-neoplastic activity in pre-clinical tumor models. Importantly, HSP90 inhibitors are predominantly being recognized as “tumor cell targeting” agents since cancer cells a) overexpress HSP90 protein, b) highly rely on HSP90 function for maintaining oncogenic signaling, and c) HSP90 inhibitors bind with high affinity to HSP90 in tumor cells. Nevertheless, results from recent studies also suggest that HSP90 inhibitors elicit anti-angiogenic properties by affecting the PI-3K/Akt/eNOS signal transduction pathway in endothelial cells, as well as through down-regulation of VEGFR-2 expression, a crucial component of the angiogenic process. In addition, blocking HSP90 may also diminish the secretion and expression of tumor cell-derived pro-angiogenic growth factors and cytokines, thus leading to “indirect” anti-angiogenic effects. This review article focuses on the role of HSP90 in angiogenesis and on delineating the effects of HSP90 inhibitors on angiogenic signaling pathways involved in tumor vascularization.
Keywords: Heat shock protein 90, angiogenesis, cancer, endothelial cells, resistance.
Current Cancer Drug Targets
Title:Implication of Heat Shock Protein 90 (HSP90) in Tumor Angiogenesis: A Molecular Target for Anti-Angiogenic Therapy?
Volume: 10 Issue: 8
Author(s): K. Staufer and O. Stoeltzing
Affiliation:
Keywords: Heat shock protein 90, angiogenesis, cancer, endothelial cells, resistance.
Abstract: The inhibition of oncogenic signaling pathways has gained great interest for cancer therapy. In this context, the molecular chaperone heat shock protein 90 (HSP90) has emerged as a promising molecular target, since it is critically involved in maintaining stability, integrity and functions of key oncogenic proteins. A variety of HSP90 inhibitors have been developed in the past decade and have shown convincing anti-neoplastic activity in pre-clinical tumor models. Importantly, HSP90 inhibitors are predominantly being recognized as “tumor cell targeting” agents since cancer cells a) overexpress HSP90 protein, b) highly rely on HSP90 function for maintaining oncogenic signaling, and c) HSP90 inhibitors bind with high affinity to HSP90 in tumor cells. Nevertheless, results from recent studies also suggest that HSP90 inhibitors elicit anti-angiogenic properties by affecting the PI-3K/Akt/eNOS signal transduction pathway in endothelial cells, as well as through down-regulation of VEGFR-2 expression, a crucial component of the angiogenic process. In addition, blocking HSP90 may also diminish the secretion and expression of tumor cell-derived pro-angiogenic growth factors and cytokines, thus leading to “indirect” anti-angiogenic effects. This review article focuses on the role of HSP90 in angiogenesis and on delineating the effects of HSP90 inhibitors on angiogenic signaling pathways involved in tumor vascularization.
Export Options
About this article
Cite this article as:
Staufer K. and Stoeltzing O., Implication of Heat Shock Protein 90 (HSP90) in Tumor Angiogenesis: A Molecular Target for Anti-Angiogenic Therapy?, Current Cancer Drug Targets 2010; 10 (8) . https://dx.doi.org/10.2174/156800910793357934
DOI https://dx.doi.org/10.2174/156800910793357934 |
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
-
Long-term Exposure to Cadmium in Food and Cigarette Smoke, Liver Effects and Hepatocellular Carcinoma
Current Drug Metabolism Targeting the Immune System in Cancer
Current Pharmaceutical Biotechnology From the Design to the Clinical Application of Thromboxane Modulators
Current Pharmaceutical Design Cytochromes P450 and Skin Cancer: Role of Local Endocrine Pathways
Anti-Cancer Agents in Medicinal Chemistry Palliative Tumor Control by Trabectedin in Pediatric Advanced Sarcoma
Current Drug Therapy Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors from the Natural Origin: A Recent Perspective
Anti-Cancer Agents in Medicinal Chemistry MDM4 (MDMX) and its Transcript Variants
Current Genomics Response to HAART in Treatment-Naive HIV-Infected Patients with a Prior Diagnosis of Tuberculosis or other Opportunistic Infections
Current HIV Research Mutational Testing in Gastrointestinal Stromal Tumor
Current Cancer Drug Targets Effects of Antiretroviral Therapy on Immunity in Patients Infected with HIV
Current Pharmaceutical Design Effects of Iron Chelation in Osteosarcoma
Current Cancer Drug Targets Radiopharmaceuticals to In Vivo Characterize Adrenal Incidentalomas:The Integrated Role of Radionuclide and Radiological Techniques
Current Radiopharmaceuticals The Activating Receptors of Natural Killer Cells and Their Inter-Switching Potentials
Current Drug Targets Polypurine Reverse Hoogsteen Hairpins as a Gene Silencing Tool for Cancer
Current Medicinal Chemistry Emerging Therapies Targeting Tumor Vasculature in Multiple Myeloma and other Hematologic and Solid Malignancies
Current Cancer Drug Targets Nano Approaches to Enhance Pharmacokinetic and Pharmacodynamic Activity of Plant Origin Drugs
Current Nanoscience Naphthalimides and Azonafides as Promising Anti-Cancer Agents
Current Medicinal Chemistry Rapamycin-loaded Immunoliposomes Functionalized with Trastuzumab: A Strategy to Enhance Cytotoxicity to HER2-positive Breast Cancer Cells
Anti-Cancer Agents in Medicinal Chemistry Hypoxia-Inducible Factors and Sphingosine 1-Phosphate Signaling
Anti-Cancer Agents in Medicinal Chemistry Four Major Factors Regulate Phosphatidylinositol 3-kinase Signaling Pathway in Cancers Induced by Infection of Human Papillomaviruses
Current Medicinal Chemistry