Abstract
Reverse Transcriptase (RT) activity is historically associated with the replication of infectious retroviruses. Cellular RT-coding genes have subsequently been identified in eukaryotic genomes. These genes are harbored within retrotransposable elements (retrotransposons and endogenous retroviruses), mobile DNA sequences characterized by the ability to integrate in mammalian genomes through RNA intermediates. Retrotransposition is mediated by an RT activity that catalyzes the reverse transcription of RNA into cDNA copies. A vast body of correlative evidence links up-regulated RT activity to cell systems with a high proliferative potential and low differentiation level, including embryonic tissues and tumors. In contrast, RT is silenced, or expressed at low levels, in differentiated cells. In recent work, we have used non-nucleosidic RT inhibitors widely employed to treat HIV infection and we have observed that these molecules exert a powerful cytostatic and differentiating activity in several models of human cancers both in vitro and in vivo, associated with the inhibition of endogenous RT activity. This review addresses the potential role of RT inhibitors as new anticancer therapeutic drugs. Based on preclinical observations, we also discuss the working hypothesis that the differentiating activity of RT inhibitors may re-establish or improve the efficacy of conventional treatments in specific conditions, such as hormone-refractory prostate carcinoma, anaplastic thyroid tumors and hematological malignancies. These novel findings strongly support the need for clinical trials to test the anti-tumor activity of RT inhibitors in specific malignancies.
Keywords: Reverse transcriptase, RT inhibitors, Differentiation, Prostate tumor, Hormone therapy, Anaplastic thyroid tumor, Radiometabolic therapy, Hematological malignancies
Current Pharmaceutical Design
Title: Anti-Tumor Activity of Non-Nucleosidic Reverse Transcriptase Inhibitors
Volume: 13 Issue: 7
Author(s): Matteo Landriscina, Corrado Spadafora, Mauro Cignarelli and Carlo Barone
Affiliation:
Keywords: Reverse transcriptase, RT inhibitors, Differentiation, Prostate tumor, Hormone therapy, Anaplastic thyroid tumor, Radiometabolic therapy, Hematological malignancies
Abstract: Reverse Transcriptase (RT) activity is historically associated with the replication of infectious retroviruses. Cellular RT-coding genes have subsequently been identified in eukaryotic genomes. These genes are harbored within retrotransposable elements (retrotransposons and endogenous retroviruses), mobile DNA sequences characterized by the ability to integrate in mammalian genomes through RNA intermediates. Retrotransposition is mediated by an RT activity that catalyzes the reverse transcription of RNA into cDNA copies. A vast body of correlative evidence links up-regulated RT activity to cell systems with a high proliferative potential and low differentiation level, including embryonic tissues and tumors. In contrast, RT is silenced, or expressed at low levels, in differentiated cells. In recent work, we have used non-nucleosidic RT inhibitors widely employed to treat HIV infection and we have observed that these molecules exert a powerful cytostatic and differentiating activity in several models of human cancers both in vitro and in vivo, associated with the inhibition of endogenous RT activity. This review addresses the potential role of RT inhibitors as new anticancer therapeutic drugs. Based on preclinical observations, we also discuss the working hypothesis that the differentiating activity of RT inhibitors may re-establish or improve the efficacy of conventional treatments in specific conditions, such as hormone-refractory prostate carcinoma, anaplastic thyroid tumors and hematological malignancies. These novel findings strongly support the need for clinical trials to test the anti-tumor activity of RT inhibitors in specific malignancies.
Export Options
About this article
Cite this article as:
Landriscina Matteo, Spadafora Corrado, Cignarelli Mauro and Barone Carlo, Anti-Tumor Activity of Non-Nucleosidic Reverse Transcriptase Inhibitors, Current Pharmaceutical Design 2007; 13 (7) . https://dx.doi.org/10.2174/138161207780249191
DOI https://dx.doi.org/10.2174/138161207780249191 |
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
-
Antibody-Targeted RNase Fusion Proteins (ImmunoRNases) for Cancer Therapy
Current Pharmaceutical Biotechnology Phytocompounds from the Medicinal and Dietary Plants: Multi-target Agents for Cervical Cancer Prevention and Therapy
Current Medicinal Chemistry Histone Deacetylase Inhibitors: An Attractive Strategy for Cancer Therapy
Current Medicinal Chemistry Reversal of Resistance to Oxazaphosphorines
Current Cancer Drug Targets PLK1 Inhibition: Prospective Role for the Treatment of Pediatric Tumors
Current Drug Targets Non-Transferrin Bound Iron - Determination in Biological Material and Clinical Implications
Current Pharmaceutical Analysis Bismuth-213 and Actinium-225 – Generator Performance and Evolving Therapeutic Applications of Two Generator-Derived Alpha-Emitting Radioisotopes
Current Radiopharmaceuticals Novel Therapeutic Approaches to Regulate Human Dihydrofolate Reductase Activity and Expression
Current Enzyme Inhibition Recent Patents on Thiazole Derivatives Endowed with Antitumor Activity
Recent Patents on Anti-Cancer Drug Discovery MicroRNA-34 Family, Mechanisms of Action in Cancer: A Review
Current Cancer Drug Targets The Role of Apoptosis in Cancer Development and Treatment: Focusing on the Development and Treatment of Hematologic Malignancies
Current Pharmaceutical Design Editorial [Hot Topic:Targeted Therapeutics – From Chemical Structures to Diagnostic and Therapeutic Agents(Executive Editor: Christine Armbruster)]
Current Pharmaceutical Design Patents Related to Cancer Stem Cell Research
Recent Patents on DNA & Gene Sequences Myelodysplastic Syndromes: Review of Pathophysiology and Current Novel Treatment Approaches
Current Cancer Drug Targets BIBR 1532 Increases Arsenic Trioxide-mediated Apoptosis in Acute Promyelocytic Leukemia Cells: Therapeutic Potential for APL
Anti-Cancer Agents in Medicinal Chemistry Targeting Tyrosine Kinase Receptors in Hepatocellular Carcinoma
Current Cancer Drug Targets Immunomodulatory Activity of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Multi-Kinase Inhibitors
Current Medicinal Chemistry Ribonucleases and ImmunoRNases as Anticancer Drugs
Current Pharmaceutical Design Clinical Presentation, Outcome and Risk Factors of Late-Onset Non- Infectious Pulmonary Complications After Allogeneic Stem Cell Transplantation
Current Stem Cell Research & Therapy