Abstract
Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α subunits, which is activated in response to reduced O2 availability. HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. Increased HIF-1α levels, as determined by immunohistochemical analysis of tumor biopsy specimens, is associated with increased mortality in many human cancers. Drugs that inhibit HIF-1 activity and have anti-cancer effects in vivo have been identified and clinical trials are warranted to establish the contexts in which addition of such agents to therapy protocols will result in increased patient survival.
Keywords: Angiogenesis, cancer, chemotherapy, hypoxia-inducible factor, invasion, metastasis, metronomic therapy, oxygen
Current Pharmaceutical Design
Title: HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery
Volume: 15 Issue: 33
Author(s): G. L. Semenza
Affiliation:
Keywords: Angiogenesis, cancer, chemotherapy, hypoxia-inducible factor, invasion, metastasis, metronomic therapy, oxygen
Abstract: Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric protein composed of HIF-1α and HIF-1α subunits, which is activated in response to reduced O2 availability. HIF-1 transactivates genes encoding proteins that are involved in key aspects of the cancer phenotype, including cell immortalization and de-differentiation, stem cell maintenance, genetic instability, glucose uptake and metabolism, pH regulation, autocrine growth/survival, angiogenesis, invasion/metastasis, and resistance to chemotherapy. Increased HIF-1α levels, as determined by immunohistochemical analysis of tumor biopsy specimens, is associated with increased mortality in many human cancers. Drugs that inhibit HIF-1 activity and have anti-cancer effects in vivo have been identified and clinical trials are warranted to establish the contexts in which addition of such agents to therapy protocols will result in increased patient survival.
Export Options
About this article
Cite this article as:
Semenza L. G., HIF-1 Inhibitors for Cancer Therapy: From Gene Expression to Drug Discovery, Current Pharmaceutical Design 2009; 15 (33) . https://dx.doi.org/10.2174/138161209789649402
DOI https://dx.doi.org/10.2174/138161209789649402 |
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
-
Targeted Drug Delivery for Breast Cancer Treatment
Recent Patents on Anti-Cancer Drug Discovery Current Approaches to Prevention of Contrast Induced Acute Kidney Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry New Trends of Deep Learning in Clinical Cardiology
Current Bioinformatics Advances in Development of Phosphatidylinositol 3-Kinase Inhibitors
Current Medicinal Chemistry Empagliflozin for Type 2 Diabetes Mellitus: An Overview of Phase 3 Clinical Trials
Current Diabetes Reviews The Role of the Novel Adipocyte-Derived Protein Adiponectin in Human Disease: An Update
Mini-Reviews in Medicinal Chemistry Cognitive and Functional Influences of Vildagliptin, a DPP-4 Inhibitor, Added to Ongoing Metformin Therapy in Elderly with Type 2 Diabetes
Endocrine, Metabolic & Immune Disorders - Drug Targets Mineralocorticoid Receptor Antagonism and Cardiac Remodeling in Ischemic Heart Failure
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Oxidative Stress and Cardiac Remodeling: An Updated Edge
Current Cardiology Reviews MicroRNA-34a Promotes Cardiomyocyte Apoptosis Post Myocardial Infarction Through Down-regulating Aldehyde Dehydrogenase 2
Current Pharmaceutical Design G Protein-Coupled Receptor Fusion Proteins in Drug Discovery
Current Pharmaceutical Design The Mevalonate Pathway as a Therapeutic Target in the Ph-Negative Chronic Myeloproliferative Disorders
Current Drug Targets Calcium Channels and Prostate Cancer
Recent Patents on Anti-Cancer Drug Discovery Cardiovascular-Active Venom Toxins: An Overview
Current Medicinal Chemistry Amyloid β -Protein Assembly as a Therapeutic Target of Alzheimers Disease
Current Pharmaceutical Design Pleiotropic Effects of Omega-3 Fatty Acids
Recent Patents on Endocrine, Metabolic & Immune Drug Discovery Therapeutic Use of Vitamin D and its Analogues in Autoimmunity
Recent Patents on Inflammation & Allergy Drug Discovery Meet Our Editorial Board Member:
Current Vascular Pharmacology Cellular and Subcellular Imaging in Live Mice Using Fluorescent Proteins
Current Pharmaceutical Biotechnology Early Growth Response-1 (EGR-1) – A Key player in Myocardial Cell Injury
Cardiovascular & Hematological Agents in Medicinal Chemistry