Abstract
Certain cancers may be auxotrophic for a particular amino acid, and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and some renal cell cancers. Arginine can be degraded by several enzymes including arginine deiminase (ADI). Although ADI is a microbial enzyme from mycoplasma, it has high affinity to arginine and catalyzes arginine to citrulline and ammonia. Citrulline can be recycled back to arginine in normal cells which express ASS, whereas ASS(-) tumor cells cannot. A pegylated form of ADI (ADI-PEG20) has been formulated and has shown in vitro and in vivo activity against melanoma and hepatocellular carcinoma. ADI-PEG20 induces apoptosis in melanoma cell lines. However, arginine deprivation can also induce ASS expression in certain melanoma cell lines which can lead to in vitro drug resistance. Phase I and II clinical trials with ADI-PEG20 have been conducted in patients with melanoma and hepatocellular carcinoma, and antitumor activity has been demonstrated in both cancers. This article reviews our laboratory and clinical experience as well as that from others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed.
Keywords: Arginine, melanoma, arginine deiminase, hepatocellular carcinoma
Current Pharmaceutical Design
Title: Arginine Deprivation as a Targeted Therapy for Cancer
Volume: 14 Issue: 11
Author(s): L. Feun, M. You, C. J. Wu, M. T. Kuo, M. Wangpaichitr, S. Spector and N. Savaraj
Affiliation:
Keywords: Arginine, melanoma, arginine deiminase, hepatocellular carcinoma
Abstract: Certain cancers may be auxotrophic for a particular amino acid, and amino acid deprivation is one method to treat these tumors. Arginine deprivation is a novel approach to target tumors which lack argininosuccinate synthetase (ASS) expression. ASS is a key enzyme which converts citrulline to arginine. Tumors which usually do not express ASS include melanoma, hepatocellular carcinoma, some mesotheliomas and some renal cell cancers. Arginine can be degraded by several enzymes including arginine deiminase (ADI). Although ADI is a microbial enzyme from mycoplasma, it has high affinity to arginine and catalyzes arginine to citrulline and ammonia. Citrulline can be recycled back to arginine in normal cells which express ASS, whereas ASS(-) tumor cells cannot. A pegylated form of ADI (ADI-PEG20) has been formulated and has shown in vitro and in vivo activity against melanoma and hepatocellular carcinoma. ADI-PEG20 induces apoptosis in melanoma cell lines. However, arginine deprivation can also induce ASS expression in certain melanoma cell lines which can lead to in vitro drug resistance. Phase I and II clinical trials with ADI-PEG20 have been conducted in patients with melanoma and hepatocellular carcinoma, and antitumor activity has been demonstrated in both cancers. This article reviews our laboratory and clinical experience as well as that from others with ADI-PEG20 as an antineoplastic agent. Future direction in utilizing this agent is also discussed.
Export Options
About this article
Cite this article as:
Feun L., You M., Wu J. C., Kuo T. M., Wangpaichitr M., Spector S. and Savaraj N., Arginine Deprivation as a Targeted Therapy for Cancer, Current Pharmaceutical Design 2008; 14 (11) . https://dx.doi.org/10.2174/138161208784246199
DOI https://dx.doi.org/10.2174/138161208784246199 |
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
-
Bisphosphonates: Molecular Mechanisms of Action and Effects on Bone Cells, Monocytes and Macrophages
Current Pharmaceutical Design Targeting the Tumor Proteasome as a Mechanism to Control the Synthesis and Bioactivity of Matrix Macromolecules
Current Molecular Medicine Meta Analysis of Advanced Cancer Survival Data Using Lognormal Parametric Fitting: A Statistical Method to Identify Effective Treatment Protocols
Current Pharmaceutical Design Imaging Methods in Gene Therapy of Cancer
Current Gene Therapy Disruption of Metabolic Pathways - Perspectives for the Treatment of Cancer
Current Cancer Drug Targets Tumor Treating Fields – Behind and Beyond Inhibiting the Cancer Cell Cycle
CNS & Neurological Disorders - Drug Targets Interferon Therapy in Lung Cancer: Current Perspectives
Current Cancer Therapy Reviews Bortezomib Enhances the Antitumor Effects of Interferon-β Gene Transfer on Melanoma Cells
Anti-Cancer Agents in Medicinal Chemistry Circulating Biomarkers for Tumor Angiogenesis: Where Are We?
Current Medicinal Chemistry Anticancer Properties of Amino Acid and Peptide Derivatives of Mycophenolic Acid
Anti-Cancer Agents in Medicinal Chemistry Therapeutic Value of Black Seed Oil in Methotrexate Hepatotoxicity in Egyptian Children with Acute Lymphoblastic Leukemia
Infectious Disorders - Drug Targets Mucosal T Cell Proliferation and Apoptosis in Inflammatory Bowel Disease
Current Drug Targets Cyclotron Production of PET Radiometals in Liquid Targets: Aspects and Prospects
Current Radiopharmaceuticals Valproic Acid in the Complex Therapy of Malignant Tumors
Current Drug Targets Neuroprotective Effects of Melanocortins in CNS Injury
Current Pharmaceutical Design Harnessing Phage Display for the Discovery of Peptide-Based Drugs and Monoclonal Antibodies
Current Medicinal Chemistry Protective Effect of NSAIDs on Cancer and Influence of COX-2 C G Genotype
Current Cancer Drug Targets Lung Cancer: Are we up to the Challenge?
Current Genomics Molecular and Cellular Activities of Vitamin E Analogues
Mini-Reviews in Medicinal Chemistry Editorial [Hot Topic: Inflammation as Target for Pharmaceutical Intervention in Cancer (Executive Editors: R.M. Schiffelers and K.E. de Visser)]
Current Pharmaceutical Design