Abstract
The treatment of cancer with common anti-proliferative agents generally suffers from an insufficient differentiation between normal and malignant cells which results in extensive side effects. To enhance the efficacy and reduce the normal tissue toxicity of anticancer drugs, numerous selective tumor therapies have emerged including the highly promising approaches ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy) and PMT (Prodrug Monotherapy). These allow a selective release of cytotoxic agents from non-toxic prodrugs at the tumor site either by targeted antibody-enzyme conjugates, enzyme encoding genes or by exploiting physiological and metabolic aberrations in cancerous tissue. Herein, recent developments in the design and biological evaluation of prodrugs for use in ADEPT, GDEPT and PMT are reviewed. As a highlight, a series of novel glycosidic prodrugs based on the natural antibiotics CC-1065 and the duocarmycins will be discussed which show a therapeutic window of up to one million. Notably, the corresponding drugs have tremendously high cytotoxicities with IC50 values of down to 110 fM.
Keywords: Prodrugs, cancer, ADEPT, GDEPT, PMT, CC-1065, duocarmycins, glycosides, hypoxia, hepatotoxicity
Current Pharmaceutical Design
Title: Prodrugs for Targeted Tumor Therapies: Recent Developments in ADEPT, GDEPT and PMT
Volume: 17 Issue: 32
Author(s): Lutz F. Tietze and Kianga Schmuck
Affiliation:
Keywords: Prodrugs, cancer, ADEPT, GDEPT, PMT, CC-1065, duocarmycins, glycosides, hypoxia, hepatotoxicity
Abstract: The treatment of cancer with common anti-proliferative agents generally suffers from an insufficient differentiation between normal and malignant cells which results in extensive side effects. To enhance the efficacy and reduce the normal tissue toxicity of anticancer drugs, numerous selective tumor therapies have emerged including the highly promising approaches ADEPT (Antibody-Directed Enzyme Prodrug Therapy), GDEPT (Gene-Directed Enzyme Prodrug Therapy) and PMT (Prodrug Monotherapy). These allow a selective release of cytotoxic agents from non-toxic prodrugs at the tumor site either by targeted antibody-enzyme conjugates, enzyme encoding genes or by exploiting physiological and metabolic aberrations in cancerous tissue. Herein, recent developments in the design and biological evaluation of prodrugs for use in ADEPT, GDEPT and PMT are reviewed. As a highlight, a series of novel glycosidic prodrugs based on the natural antibiotics CC-1065 and the duocarmycins will be discussed which show a therapeutic window of up to one million. Notably, the corresponding drugs have tremendously high cytotoxicities with IC50 values of down to 110 fM.
Export Options
About this article
Cite this article as:
F. Tietze Lutz and Schmuck Kianga, Prodrugs for Targeted Tumor Therapies: Recent Developments in ADEPT, GDEPT and PMT, Current Pharmaceutical Design 2011; 17 (32) . https://dx.doi.org/10.2174/138161211798194459
DOI https://dx.doi.org/10.2174/138161211798194459 |
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
-
Modulatory Potential of <i>Citrus sinensis</i> and <i>Moringa oleifera</i> Extracts and
Epiphytes on Rat Liver Mitochondrial Permeability Transition Pore
Current Drug Discovery Technologies Endoglin (CD105): A Target for Anti-angiogenetic Cancer Therapy
Current Drug Targets Insects Antiviral and Anticancer Peptides: New Leads for the Future?
Protein & Peptide Letters An Update on Developments in Female Hormonal Contraception
Current Women`s Health Reviews The Role of CD40 Expression in Dendritic Cells in Cancer Biology; A Systematic Review
Current Cancer Drug Targets Recent Advances in Biotransformation by Cunninghamella Species
Current Drug Metabolism Perspectives on Chemopreventive and Therapeutic Potential of Curcumin Analogs in Medicinal Chemistry
Mini-Reviews in Medicinal Chemistry DNA Repair Inhibitors: The Next Major Step to Improve Cancer Therapy
Current Topics in Medicinal Chemistry Evaluation of Non-Coding RNAs as Potential Targets in Head and Neck Squamous Cell Carcinoma Cancer Stem Cells
Current Drug Targets The FDG-PET Revolution of Medical Imaging – Four Decades and Beyond
Current Molecular Imaging (Discontinued) Inhibitors of the Immunoproteasome: Current Status and Future Directions
Current Pharmaceutical Design Advances in Colloidal Processing of Rare Earth Particles
Current Smart Materials (Discontinued) Advanced Approaches of Bioactive Peptide Molecules and Protein Drug Delivery Systems
Current Pharmaceutical Design Targeted Inhibition of Rictor/mTORC2 in Cancer Treatment: A New Era after Rapamycin
Current Cancer Drug Targets Role of microRNAs in Gynecological Pathology
Current Medicinal Chemistry Breast Cancer Diagnosis Using Data Mining Methods, Cumulative Histogram Features, and Gary Level Co-occurrence Matrix
Current Medical Imaging Voltage-Gated Sodium Channel Blockers as Immunomodulators
Recent Patents on CNS Drug Discovery (Discontinued) The Cyclin-Dependent Kinase Inhibitor p21CDKN1A as a Target of Anti-Cancer Drugs
Current Cancer Drug Targets Hitting the Golden TORget: Curcumin’s Effects on mTOR Signaling
Anti-Cancer Agents in Medicinal Chemistry The Balancing Act between Colonisers and Inflammation: T regulatory and TH17 Cells in Mucosal Immunity during Otitis Media
Current Immunology Reviews (Discontinued)