Abstract
For the last twenty years, significant progress in Molecular and Cellular Biology has resulted in a better characterization and understanding of the biology and prognosis of acute myeloid leukemia (AML). These achievements have provided new opportunities for the development of innovative, more effective therapies. Novel agents potentially useful in the treatment of patients with AML include new formulations of established drugs, newer nucleoside analogs, molecular target drugs, monoclonal antibodies and other agents. Three newer nucleoside analogs, clofarabine, troxacitabine and sapacitabine have been recently investigated in patients with AML. Two methylation inhibitors, 5-azacyticline and decitabine are pyrimidine nucleoside analogs of cytidine which can be incorporated into RNA and/or DNA. Lower doses of these agents are active in AML and have been extensively investigated, especially in secondary AML and AML in elderly patients. Tipifarnib and lonafarnib are orally available farnesyltransferase inhibitors with in vitro and in vivo activity against AML. In recent years, FLT3 inhibitors, lestaurinib, tandutinib and PKC 412 have been developed and tested in AML. The preclinical observations and clinical studies indicate that FLT3 inhibitors are promising agents in the treatment of FLT3 mutated AML patients, especially when used in combinations with chemotherapy. Several newer MDR inhibitors, including valspodar (PSC-833) and zosuquidar trihydrochloride have been also tested for the treatment of relapsed AML. This article reviews the various classes of AML targets and drugs that are under early phase clinical evaluation, especially those that are likely to enter clinical practice in the near future.
Keywords: AML, liposomal daunorubicin, nucleoside analogs, hypomethylating agents, histone deacetylase inhibitors, farnesyltransferase inhibitors, mTOR kinase inhibitors, monoclonal antibodies
Current Medicinal Chemistry
Title: Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity
Volume: 18 Issue: 5
Author(s): T. Robak, A. Szmigielska-Kaplon, A. Pluta, O. Grzybowska-Izydorczyk, A. Wolska, M. Czemerska and A Wierzbowska
Affiliation:
Keywords: AML, liposomal daunorubicin, nucleoside analogs, hypomethylating agents, histone deacetylase inhibitors, farnesyltransferase inhibitors, mTOR kinase inhibitors, monoclonal antibodies
Abstract: For the last twenty years, significant progress in Molecular and Cellular Biology has resulted in a better characterization and understanding of the biology and prognosis of acute myeloid leukemia (AML). These achievements have provided new opportunities for the development of innovative, more effective therapies. Novel agents potentially useful in the treatment of patients with AML include new formulations of established drugs, newer nucleoside analogs, molecular target drugs, monoclonal antibodies and other agents. Three newer nucleoside analogs, clofarabine, troxacitabine and sapacitabine have been recently investigated in patients with AML. Two methylation inhibitors, 5-azacyticline and decitabine are pyrimidine nucleoside analogs of cytidine which can be incorporated into RNA and/or DNA. Lower doses of these agents are active in AML and have been extensively investigated, especially in secondary AML and AML in elderly patients. Tipifarnib and lonafarnib are orally available farnesyltransferase inhibitors with in vitro and in vivo activity against AML. In recent years, FLT3 inhibitors, lestaurinib, tandutinib and PKC 412 have been developed and tested in AML. The preclinical observations and clinical studies indicate that FLT3 inhibitors are promising agents in the treatment of FLT3 mutated AML patients, especially when used in combinations with chemotherapy. Several newer MDR inhibitors, including valspodar (PSC-833) and zosuquidar trihydrochloride have been also tested for the treatment of relapsed AML. This article reviews the various classes of AML targets and drugs that are under early phase clinical evaluation, especially those that are likely to enter clinical practice in the near future.
Export Options
About this article
Cite this article as:
Robak T., Szmigielska-Kaplon A., Pluta A., Grzybowska-Izydorczyk O., Wolska A., Czemerska M. and Wierzbowska A, Novel and Emerging Drugs for Acute Myeloid Leukemia: Pharmacology and Therapeutic Activity, Current Medicinal Chemistry 2011; 18 (5) . https://dx.doi.org/10.2174/092986711794480104
DOI https://dx.doi.org/10.2174/092986711794480104 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
Call for Papers in Thematic Issues
Advances in Medicinal Chemistry: From Cancer to Chronic Diseases.
The broad spectrum of the issue will provide a comprehensive overview of emerging trends, novel therapeutic interventions, and translational insights that impact modern medicine. The primary focus will be diseases of global concern, including cancer, chronic pain, metabolic disorders, and autoimmune conditions, providing a broad overview of the advancements in ...read more
Cellular and Molecular Mechanisms of Non-Infectious Inflammatory Diseases: Focus on Clinical Implications
The Special Issue covers the results of the studies on cellular and molecular mechanisms of non-infectious inflammatory diseases, in particular, autoimmune rheumatic diseases, atherosclerotic cardiovascular disease and other age-related disorders such as type II diabetes, cancer, neurodegenerative disorders, etc. Review and research articles as well as methodology papers that summarize ...read more
Chalcogen-modified nucleic acid analogues
Chalcogen-modified nucleosides, nucleotides and oligonucleotides have been of great interest to scientific research for many years. The replacement of oxygen in the nucleobase, sugar or phosphate backbone by chalcogen atoms (sulfur, selenium, tellurium) gives these biomolecules unique properties resulting from their altered physical and chemical properties. The continuing interest in ...read more
Current advances in inherited cardiomyopathy
Describe in detail all novel advances in multimodality imaging related to inherited cardiomyopathy diagnosis and prognosis. Shed light to deeper phenotypic characterization. Acknowledge recent advances in genetics, genomics and precision medicineread 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
-
Pharmacologic Treatment of Pulmonary Arterial Hypertension
Current Pharmaceutical Design Can Antidiabetic Drugs Improve Male Reproductive (Dys)Function Associated with Diabetes?
Current Medicinal Chemistry Metabolic Syndrome and Non-Cardiac Vascular Diseases: An Update from Human Studies
Current Pharmaceutical Design Immunotherapy in Invasive Fungal Infection - Focus on Invasive Aspergillosis
Current Pharmaceutical Design Low Dose Chest Computed Tomography, in Identifying Pulmonary Complications in Immunocompromised Patients After Allogeneic Hematopoietic Stem Cell Transplantation
Current Respiratory Medicine Reviews Optimizing Conventional Medical Therapies in Inflammatory Bowel Disease in 2014
Current Drug Targets Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews Acute Myeloid Leukemia in the Elderly: Current Therapeutic Results and Perspectives for Clinical Research
Reviews on Recent Clinical Trials Importance of Metabolic Activation Study to the Safe Use of Chinese Herbal Medicines
Current Drug Metabolism Pharmacogenetics of Childhood Acute Lymphoblastic Leukemia
Current Pharmacogenomics Intravenous Immunoglobulin Preparations and Autoimmune Disorders: Mechanisms of Action
Current Pharmaceutical Biotechnology Cellular Therapy of Lysosomal Storage Disorders: Current Status and Future Prospects
Current Pediatric Reviews Role of Redox Homeostasis and Inflammation in the Pathogenesis of Pulmonary Arterial Hypertension
Current Medicinal Chemistry Decreasing Systemic Toxicity Via Transdermal Delivery of Anticancer Drugs
Current Drug Metabolism Old Drugs-Current Perspectives
Current Pharmacogenomics Acute Renal Failure in Different Malignant Tumors
Current Medicinal Chemistry Current Concepts of Mechanisms in Drug-Induced Hepatotoxicity
Current Medicinal Chemistry Antibody Based Therapies in Acute Leukemia
Current Drug Targets Nonstandard Drugs and Feasible New Interventions for Autoimmune Hepatitis: Part I
Inflammation & Allergy - Drug Targets (Discontinued) Mechanism-Based Inhibitors from Phytomedicine: Risks of Hepatotoxicity and their Potential Hepatotoxic Substructures
Current Drug Metabolism