Abstract
Hsp90 (heat shock protein 90) is a molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory, metabolism, organization, and signaling proteins. Binding to Hsp90 is required for normal function of many proteins. In addition, Hsp90 has an extra-cellular function. It is found in two isotypes: α which is inducible and β which is constitutive. Tumor cells frequently over express Hsp90α, and Hsp90 is implicated in cancer progression. Hence Hsp90 has emerged as a potential target for cancer treatment. A variety of agents have been found to interfere with Hsp function, mainly by binding to an ATP binding site on the molecule. More recent agents interfere with protein binding or the dimerization of Hsp90 needed for function. Preclinical studies have demonstrated that disruption of the many client proteins chaperoned by Hsp90 is achievable and associated with significant growth inhibition, both in vitro and in tumor xenografts. As a result, agents which interfere with this proteins function are being tested in the clinic as a targeted method of interfering with malignant growth. We review the current clinical status of therapeutic efforts to perturb this pathway and discuss future directions.
Keywords: HSP90, inhibitor, signal transduction, clinical trials
Current Cancer Drug Targets
Title: The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target
Volume: 8 Issue: 6
Author(s): M. F. Barginear, C. Van Poznak, N. Rosen, S. Modi, C. A. Hudis and D. R. Budman
Affiliation:
Keywords: HSP90, inhibitor, signal transduction, clinical trials
Abstract: Hsp90 (heat shock protein 90) is a molecular chaperone that modulates the stability and/or transport of a diverse set of critical cellular regulatory, metabolism, organization, and signaling proteins. Binding to Hsp90 is required for normal function of many proteins. In addition, Hsp90 has an extra-cellular function. It is found in two isotypes: α which is inducible and β which is constitutive. Tumor cells frequently over express Hsp90α, and Hsp90 is implicated in cancer progression. Hence Hsp90 has emerged as a potential target for cancer treatment. A variety of agents have been found to interfere with Hsp function, mainly by binding to an ATP binding site on the molecule. More recent agents interfere with protein binding or the dimerization of Hsp90 needed for function. Preclinical studies have demonstrated that disruption of the many client proteins chaperoned by Hsp90 is achievable and associated with significant growth inhibition, both in vitro and in tumor xenografts. As a result, agents which interfere with this proteins function are being tested in the clinic as a targeted method of interfering with malignant growth. We review the current clinical status of therapeutic efforts to perturb this pathway and discuss future directions.
Export Options
About this article
Cite this article as:
Barginear F. M., Van Poznak C., Rosen N., Modi S., Hudis A. C. and Budman R. D., The Heat Shock Protein 90 Chaperone Complex: An Evolving Therapeutic Target, Current Cancer Drug Targets 2008; 8 (6) . https://dx.doi.org/10.2174/156800908785699379
DOI https://dx.doi.org/10.2174/156800908785699379 |
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
-
Pathobiology of Head and Neck Squamous Tumorigenesis
Current Cancer Drug Targets Recent Developments Towards the Synthesis of Varitriol: An Antitumour Agent from Marine Derived Fungus Emericella Variecolor
Current Organic Synthesis SPECT-CT and PET-CT in Oncology - An Overview
Current Medical Imaging Toll-Like Receptors and Human Disease: Lessons from Single Nucleotide Polymorphisms
Current Genomics Synthesis, Biological Evaluation, Molecular Docking Study and Acute Oral Toxicity Study of Coupled Imidazole-Pyrimidine Derivatives
Letters in Drug Design & Discovery LRIGs: A Prognostically Significant Family with Emerging Therapeutic Competence against Cancers
Current Cancer Drug Targets The Use of Oncolytic Vaccinia Viruses in the Treatment of Cancer: A New Role for an Old Ally?
Current Gene Therapy Ghrelin: New Insight to Mechanisms and Treatment of Postoperative Gastric Ileus
Current Pharmaceutical Design The Pro-Survival Function of Akt Kinase can be Overridden or Altered to Contribute to Induction of Apoptosis
Current Cancer Drug Targets The Association of Very High Hair Manganese Accumulation and High Oxidative Stress in Mongolian People
Current Aging Science Electrical Impedance Scanning - A New Diagnostic Tool in Cancer Detection: Current Status and Recent Developments
Current Medical Imaging A Systems Biology Road Map for the Discovery of Drugs Targeting Cancer Cell Metabolism
Current Pharmaceutical Design Hematopoietic Growth Factors Support in the Elderly Cancer Patients Treated with Antiblastic Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Targeting Cancer Stem Cells: Promises and Challenges
Anti-Cancer Agents in Medicinal Chemistry microRNA Biogenesis Pathway as a Therapeutic Target for Human Disease and Cancer
Current Pharmaceutical Design Potential MicroRNA Targets for Cancer Chemotherapy
Current Medicinal Chemistry Solid Lipid Nanoparticles: A Promising Nanomaterial in Drug Delivery
Current Pharmaceutical Design Improving Brain Drug Targeting Through Exploitation of The Nose-to- Brain Route: A Physiological and Pharmacokinetic Perspective
Current Drug Delivery Anti-Cancer Approach with NK4: Bivalent Action and Mechanisms
Anti-Cancer Agents in Medicinal Chemistry Tapasin and Human Leukocyte Antigen Class I Dysregulation Correlates with Survival in Glioblastoma Multiforme
Anti-Cancer Agents in Medicinal Chemistry