Abstract
Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity. Telomeres are structurally unique DNA sequences at the end of human chromosomes, which play an integral role in the cellular mortality of normal cells. As telomeres shorten with successive cellular divisions, cells develop chromosomal instability and undergo either apoptosis or senescence. In many cancers, this apoptosis or senescence is avoided as normal telomere length is maintained by a ribonucleoprotein reverse transcriptase called telomerase. Telomerase is expressed in more than 85% of all cancers and confers cancerous cells with a replicative immortality, which is a hallmark of malignant tumors. In contrast, telomerase activity is not detectable in the majority of normal somatic cell populations. Therefore, the targeting of telomerase and telomere maintenance mechanisms represent a potentially promising therapeutic approach for various types of cancer. This review evaluates the roles of GRN163L, T-oligo and small molecule G-quadruplex stabilizers as potential anticancer therapies by targeting telomerase and other telomere maintenance mechanisms.
Keywords: Clinical trials, G-quadruplex, GRN163L, tankyrase, telomere, telomerase, telomerase inhibitor, T-oligo.
Current Pharmaceutical Design
Title:Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy
Volume: 20 Issue: 41
Author(s): Zachary Crees, Jennifer Girard, Zechary Rios, Gregory M. Botting, Kymberly Harrington, Caleb Shearrow, Luke Wojdyla, Amanda L. Stone, Srijayaprakash B. Uppada, Joseph T. Devito and Neelu Puri
Affiliation:
Keywords: Clinical trials, G-quadruplex, GRN163L, tankyrase, telomere, telomerase, telomerase inhibitor, T-oligo.
Abstract: Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity. Telomeres are structurally unique DNA sequences at the end of human chromosomes, which play an integral role in the cellular mortality of normal cells. As telomeres shorten with successive cellular divisions, cells develop chromosomal instability and undergo either apoptosis or senescence. In many cancers, this apoptosis or senescence is avoided as normal telomere length is maintained by a ribonucleoprotein reverse transcriptase called telomerase. Telomerase is expressed in more than 85% of all cancers and confers cancerous cells with a replicative immortality, which is a hallmark of malignant tumors. In contrast, telomerase activity is not detectable in the majority of normal somatic cell populations. Therefore, the targeting of telomerase and telomere maintenance mechanisms represent a potentially promising therapeutic approach for various types of cancer. This review evaluates the roles of GRN163L, T-oligo and small molecule G-quadruplex stabilizers as potential anticancer therapies by targeting telomerase and other telomere maintenance mechanisms.
Export Options
About this article
Cite this article as:
Crees Zachary, Girard Jennifer, Rios Zechary, Botting M. Gregory, Harrington Kymberly, Shearrow Caleb, Wojdyla Luke, Stone L. Amanda, Uppada B. Srijayaprakash, Devito T. Joseph and Puri Neelu, Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy, Current Pharmaceutical Design 2014; 20 (41) . https://dx.doi.org/10.2174/1381612820666140630100702
DOI https://dx.doi.org/10.2174/1381612820666140630100702 |
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
-
Hydrogen Sulfide Regulates Intracellular Ca2+ Concentration in Endothelial Cells From Excised Rat Aorta
Current Pharmaceutical Biotechnology Current and Future Scenario of Immunotherapy for the Treatment of Hepatocellular Carcinoma
Current Cancer Therapy Reviews Novel Options for the Pharmacological Treatment of Chronic Anal Fissure – Role of Botulin Toxin
Current Clinical Pharmacology Radiobromine-Labelled Tracers for Positron Emission Tomography: Possibilities and Pitfalls
Current Radiopharmaceuticals A Systematic Review of Genes Involved in the Inverse Resistance Relationship Between Cisplatin and Paclitaxel Chemotherapy: Role of BRCA1
Current Cancer Drug Targets Impact of Metformin on Male Reproduction
Current Pharmaceutical Design Identification of KEY lncRNAs and mRNAs Associated with Oral Squamous Cell Carcinoma Progression
Current Bioinformatics Mucoadhesive Vaginal Drug Delivery Systems
Recent Patents on Drug Delivery & Formulation Mutations of Chromatin Structure Regulating Genes in Human Malignancies
Current Protein & Peptide Science Molecular Mechanisms of Tumor Invasion and Metastasis: An Integrated View
Current Molecular Medicine Model Systems for Pulmonary Infectious Diseases: Paradigms of Anthrax and Tuberculosis
Current Topics in Medicinal Chemistry Development and Applications of Optical Imaging Techniques in Cancer Diagnosis: Diffuse Optical Tomography and Microendoscopy
Current Medical Imaging Functions of Antimicrobial Peptides in Vertebrates
Current Protein & Peptide Science The Dynamics of the Hypothalamic-Pituitary-Ovarian Axis, ReproductivePerformance and Sexuality Following Bariatric Surgery
Current Women`s Health Reviews Chalcones Incorporated Pyrazole Ring Inhibit Proliferation, Cell Cycle Progression, Angiogenesis and Induce Apoptosis of MCF7 Cell Line
Anti-Cancer Agents in Medicinal Chemistry Methodological Aspects and Applications of In Vivo Imaging of Apoptosis in Oncology: An Illustrative Review
Current Medical Imaging The Relevance of Supplemental Vitamin D in Malignancies
Anti-Cancer Agents in Medicinal Chemistry Trichostatin A - like Hydroxamate Histone Deacetylase Inhibitors as Therapeutic Agents: Toxicological Point of View
Current Medicinal Chemistry Gene Expression Analysis Approach to Establish Possible Links Between Parkinson's Disease, Cancer and Cardiovascular Diseases
CNS & Neurological Disorders - Drug Targets Histone Deacetylase Inhibitors as Potential Therapeutic Agents for the Treatment of Malignant Mesothelioma
Anti-Cancer Agents in Medicinal Chemistry