Abstract
The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoral cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.
Keywords: Cancer therapy, uPAR, ATF, saporin, diphtheria toxin, Pseudomonas exotoxin A, recombinant expression, BTLs, heterotopic toxicity, Ribosome Inactivating Proteins, immunotoxins, leukemias, antitumoral activity, endocytic receptors, potency
Current Pharmaceutical Design
Title: Urokinase Receptor (uPAR) Ligand based Recombinant Toxins for Human Cancer Therapy
Volume: 17 Issue: 19
Author(s): Maddalena de Virgilio and Franco Silvestris
Affiliation:
Keywords: Cancer therapy, uPAR, ATF, saporin, diphtheria toxin, Pseudomonas exotoxin A, recombinant expression, BTLs, heterotopic toxicity, Ribosome Inactivating Proteins, immunotoxins, leukemias, antitumoral activity, endocytic receptors, potency
Abstract: The urokinase receptor (uPAR) exerts essential functions in the pathophysiology of cancers and therefore constitutes an important drug target. In order to generate efficient drugs against uPAR, a new approach includes chimeric proteins associating one molecular address to specifically target uPAR and one bacterial or plant toxin that will eventually kill the tumoral cell. Using this frame, several recombinant toxins have been designed namely DTAT, DTAT13, EGFATFKDEL 7 mut, and ATF-SAP. As molecular address, all of these fusion proteins use the amino-terminal fragment of urokinase that binds with high affinity to uPAR through its growth factor domain (GFD). The various toxin moieties were derived from either diphtheria toxin, Pseudomonas exotoxin A (PE38), or saporin. In this review, we describe the rational, design, production and therapeutic anti-cancer potential of these chimeric toxins.
Export Options
About this article
Cite this article as:
de Virgilio Maddalena and Silvestris Franco, Urokinase Receptor (uPAR) Ligand based Recombinant Toxins for Human Cancer Therapy, Current Pharmaceutical Design 2011; 17 (19) . https://dx.doi.org/10.2174/138161211796718170
DOI https://dx.doi.org/10.2174/138161211796718170 |
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
-
Immunomodulation and Anti-inflammatory Roles of Polyphenols as Anticancer Agents
Anti-Cancer Agents in Medicinal Chemistry Effect of Non-Ionizing Electromagnetic Fields of Anthropic Origin on Male Fertility
Current Chemical Biology MATra - Magnet Assisted Transfection: Combining Nanotechnology and Magnetic Forces to Improve Intracellular Delivery of Nucleic Acids
Current Pharmaceutical Biotechnology Herpes Simplex Encephalitis: From Virus to Therapy
Infectious Disorders - Drug Targets Challenges in the Design of Clinically Useful Brain-targeted Drug Nanocarriers
Current Medicinal Chemistry A Network Biology Approach for Assessing the Role of Pathologic Adipose Tissues in Insulin Resistance Using Meta-analysis of Microarray Datasets
Current Genomics MiRNAs in Human Cancers: The Diagnostic and Therapeutic Implications
Current Pharmaceutical Design Dietary Polyphenols for Prostate Cancer Therapy
Current Bioactive Compounds CRISPR-Cas9, A Promising Therapeutic Tool for Cancer Therapy: A Review
Protein & Peptide Letters PET Imaging for Gene & Cell Therapy
Current Gene Therapy Natural Sirtuin Modulators in Drug Discovery: A Review (2010 -2020)
Current Medicinal Chemistry γ-Secretase Inhibitors and Modulators for the Treatment of Alzheimer's Disease: Disappointments and Hopes
Current Topics in Medicinal Chemistry Plant Coumestans: Recent Advances and Future Perspectives in Cancer Therapy
Anti-Cancer Agents in Medicinal Chemistry Editorial [Hot Topic: ADAMs: Targets for Drug Discovery (Executive Editor: Marcia L. Moss)]
Current Pharmaceutical Design Editorial (Thematic Issue: Implication of Non-coding RNAs in Cancer Biology and Cellular Physiology)
Current Genomics A Connecting Switch Among Aging, Diabetes and Tumor: Avenue Leading to Cancer Therapeutics
Current Cancer Therapy Reviews Drug Delivery Across the Blood-Brain Barrier
Current Nanoscience The Role of PET/CT and SPECT/CT in Oncology Drug Development
Current Molecular Imaging (Discontinued) Innovative Cancer Treatments that Augment Radiotherapy or Chemotherapy by the Use of Immunotherapy or Gene Therapy
Recent Patents on Anti-Cancer Drug Discovery Nitric Oxide is a Key Molecule Serving as a Bridge between Radiation-Induced Bystander and Adaptive Responses
Current Molecular Pharmacology