Abstract
Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.
Keywords: Heat shock protein, HSP90, Cancer, Drug, 17-AAG, 17-DMG, IP104.
Current Pharmaceutical Design
Title:Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer
Volume: 22 Issue: 20
Author(s): Absarul Haque, Qamre Alam, Mohammad Zubair Alam, Esam I. Azhar, Khalid Hussain Wali Sait, Nisrin Anfinan, Gohar Mushtaq, Mohammad Amjad Kamal and Mahmood Rasool
Affiliation:
Keywords: Heat shock protein, HSP90, Cancer, Drug, 17-AAG, 17-DMG, IP104.
Abstract: Heat Shock Protein 90 (HSP90) is a ubiquitous molecular chaperone that is considered to be the most abundantly expressed protein in various human cancers such as breast, lung, colon, prostate, leukemia and skin. The master regulator, HSP90 plays a pivotal role in the conformational stabilization, maturation and activity of its various labile oncogenic client proteins such as p53, ErbB2, Bcr-Abl, Akt, Her-2, Cdk4, Cdk6, Raf-1 and v-Src in altered cells. Hence, making a guaranteed attempt to inhibit such a master regulator for cancer therapy appears to be a potential approach for combinatorial inhibition of numerous oncogenic signaling pathways simultaneously. Considerable efforts are being under way to develop novel molecular targets and its inhibitors that may block key signaling pathways involved in the process of tumorigenesis and metastasis. In this regards, HSP90 has acquired immense interest as a potent anticancer drug-target due to its key functional link with multiple signaling pathways involved in the process of cell proliferation and cell survival. Notably, geldanamycin and its derivatives (17-AAG, 17-DMAG) have shown quite encouraging results in inhibiting HSP90 function in several cancers and currently almost 17 drug candidates known to be target HSP90 are being under clinical trials either as single agents or combinatorial therapy. Hence, this review is an attempt to get new insight into novel drug target therapy by focusing on recent advances made in understanding HSP90 chaperone structure-function relationships, identification of new HSP90 client proteins and, more importantly, on the advancements of HSP90 targeted therapy based on various existing and emerging classical inhibitors.
Export Options
About this article
Cite this article as:
Haque Absarul, Alam Qamre, Zubair Alam Mohammad, I. Azhar Esam, Hussain Wali Sait Khalid, Anfinan Nisrin, Mushtaq Gohar, Amjad Kamal Mohammad and Rasool Mahmood, Current Understanding of HSP90 as a Novel Therapeutic Target: An Emerging Approach for the Treatment of Cancer, Current Pharmaceutical Design 2016; 22 (20) . https://dx.doi.org/10.2174/1381612822666160325152200
DOI https://dx.doi.org/10.2174/1381612822666160325152200 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
- Announcements
Related Articles
-
Targeting Receptor Tyrosine Kinases Using Monoclonal Antibodies: The Most Specific Tools for Targeted-Based Cancer Therapy
Current Drug Targets Fused Xanthone Derivatives as Antiproliferative Agents
Anti-Cancer Agents in Medicinal Chemistry Radioimmunotherapy of Solid Tumors: Searching for the Right Target
Current Drug Delivery The Present and Future of Cervical Cancer Screening Programmes in Europe
Current Pharmaceutical Design 3D-QSAR Studies of Natural Steroidal Saponins as Anticancer Agents in Human Nasopharyngeal Carcinoma Epithelial Cells
Letters in Drug Design & Discovery Apoptosis: Potential Therapeutic Targets for New Drug Discovery
Current Medicinal Chemistry Small Heat Shock Proteins and the Endoplasmic Reticulum: Potential Attractive Therapeutic Targets?
Current Molecular Medicine White Poplar (Populus alba L.) Suspension Cultures as a Model System to Study Apoptosis Induced by Alfalfa Saponins
Anti-Cancer Agents in Medicinal Chemistry Augmentation Therapy with Alpha1-antitrypsin: Novel Perspectives
Cardiovascular & Hematological Disorders-Drug Targets miRNAs in Cancer Prevention and Treatment and as Molecular Targets for Natural Product Anticancer Agents
Current Cancer Drug Targets Immune Response Manipulation: Recombinant Immunoreceptors Endow T-Cells with Predefined Specificity
Current Pharmaceutical Design HIV Infection Induces Morphometrical Changes on the Oral (Buccal Mucosa and Tongue) Epithelial Cells
Current HIV Research Azathioprine in Multiple Sclerosis
Mini-Reviews in Medicinal Chemistry Sleep Duration as a Risk Factor for Cardiovascular Disease- a Review of the Recent Literature
Current Cardiology Reviews Tumor Specific Novel Taxoid-Monoclonal Antibody Conjugates
Current Medicinal Chemistry Anticancer and Antimicrobial Evaluations on Alternative Reading Frame (ARF) Peptides and their Derivatives
Protein & Peptide Letters Cucurbitacin IIb from Ibervillea sonorae Induces Apoptosis and Cell Cycle Arrest via STAT3 Inhibition
Anti-Cancer Agents in Medicinal Chemistry Biomedical Applications of Zinc Oxide Nanomaterials
Current Molecular Medicine Anti-Cancer Drug Design Using Natural and Synthetic Pharmacophores
Current Organic Chemistry Recent Studies and Biological Aspects of Substantial Indole Derivatives with Anti-cancer Activity
Current Organic Chemistry