Abstract
Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1 activation leads to the transcription of a plethora of target genes that promote physiological changes associated with therapeutic resistance, including the inhibition of apoptosis and senescence and the activation of drug efflux and cellular metabolism. As a result, targeting HIF-1 represents an attractive strategy to enhance the efficacy of current therapies as well as reduce resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have primarily focused on reducing HIF-1α protein levels, by inducing its degradation or inhibiting its transcription, inhibiting HIF-1-mediated transcription, or disrupting the formation of the HIF-1 transcription factor complex. To date, multiple preclinical and clinical agents have been identified that effectively inhibit HIF-1 activity through various mechanisms, likely accounting for a portion of their anti-tumor efficacy. This review aims to provide an overview of our current understanding of the role of HIF-1 in therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors as an anti-cancer strategy.
Keywords: HIF-1, hypoxia-inducible factor-1, hypoxia, therapeutic resistance.
Current Medicinal Chemistry
Title:HIF-1 Signaling in Drug Resistance to Chemotherapy
Volume: 21 Issue: 26
Author(s): N.A. Warfel and W.S. El-Deiry
Affiliation:
Keywords: HIF-1, hypoxia-inducible factor-1, hypoxia, therapeutic resistance.
Abstract: Activation of hypoxia-inducible factor 1 (HIF-1) signaling is observed in a broad range of human cancers due to tumor hypoxia and epigenetic mechanisms. HIF-1 activation leads to the transcription of a plethora of target genes that promote physiological changes associated with therapeutic resistance, including the inhibition of apoptosis and senescence and the activation of drug efflux and cellular metabolism. As a result, targeting HIF-1 represents an attractive strategy to enhance the efficacy of current therapies as well as reduce resistance to chemotherapy in tumors. Approaches to inhibit HIF-1 signaling have primarily focused on reducing HIF-1α protein levels, by inducing its degradation or inhibiting its transcription, inhibiting HIF-1-mediated transcription, or disrupting the formation of the HIF-1 transcription factor complex. To date, multiple preclinical and clinical agents have been identified that effectively inhibit HIF-1 activity through various mechanisms, likely accounting for a portion of their anti-tumor efficacy. This review aims to provide an overview of our current understanding of the role of HIF-1 in therapeutic resistance and discuss the ongoing effort to develop HIF-1 inhibitors as an anti-cancer strategy.
Export Options
About this article
Cite this article as:
Warfel N.A. and El-Deiry W.S., HIF-1 Signaling in Drug Resistance to Chemotherapy, Current Medicinal Chemistry 2014; 21 (26) . https://dx.doi.org/10.2174/0929867321666140414101056
DOI https://dx.doi.org/10.2174/0929867321666140414101056 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Screening Neuroprotective Agents Through 4-hydroxynonenal, Ethanol, High Glucose, Homocysteine, Okadaic Acid, Rotenone, and Oxygen-Glucose Deprivation Induced PC12 Injury Models: A Review
Current Psychopharmacology Gallium-68: A New Trend in PET Radiopharmacy
Current Radiopharmaceuticals The Role of ING Tumor Suppressors in UV Stress Response and Melanoma Progression
Current Drug Targets Hybrid PET Imaging in Neurologic Disease: PET/MRI Rather than PET/CT
Current Medical Imaging The 18 kDa Translocator Protein (TSPO): A New Perspective in Mitochondrial Biology
Current Molecular Medicine Recent Patents in Oncolytic Virotherapy
Recent Patents on Biotechnology Can Breast Cancer Stem Cells Evade the Immune System?
Current Medicinal Chemistry The use of Azoles Containing Natural Products in Cancer Prevention and Treatment: An Overview
Anti-Cancer Agents in Medicinal Chemistry Meet Our Editorial Board Member
Current Pharmacogenomics and Personalized Medicine Recent Advances in Medicinal Chemistry and Pharmaceutical Technology- Strategies for Drug Delivery to the Brain
Current Topics in Medicinal Chemistry Angiotensin II Receptor Blocker: Possibility of Antitumor Agent for Prostate Cancer
Mini-Reviews in Medicinal Chemistry The Delivery of Personalised, Precision Medicines <i>via</i> Synthetic Proteins
Drug Delivery Letters Some Implications of Receptor Kinase Signaling Pathway for Development of Multitargeted Kinase Inhibitors
Current Radiopharmaceuticals STAT3 as a Therapeutic Target for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Cannabinoid System as a Potential Target for Drug Development in the Treatment of Cardiovascular Disease
Current Vascular Pharmacology SnoN: Bridging Neurobiology and Cancer Biology
Current Molecular Medicine Targeting Stem Cells-Clinical Implications for Cancer Therapy
Current Stem Cell Research & Therapy Tumor-Targeting Peptides: Ligands for Molecular Imaging and Therapy
Anti-Cancer Agents in Medicinal Chemistry CB Receptor Ligands from Plants
Current Topics in Medicinal Chemistry Nanoparticles: A Neurotoxicological Perspective
CNS & Neurological Disorders - Drug Targets