Abstract
Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilize the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clinical results observed in the last years, the long-term effects of imatinib and its ability to completely eradicate CML are still unknown. Moreover, similar to many other anti-cancer drugs, clinical resistance to imatinib has emerged. In this review we will discuss the in vitro and in vivo results obtained with the novel tyrosine kinase inhibitors developed to overcome imatinib resistance in Bcr-Abl expressing hematologiocal disorders.
Keywords: Bcr-Abl, chronic myelogenous leukemia, tyrosine kinase inhibitors
Anti-Cancer Agents in Medicinal Chemistry
Title: Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia
Volume: 9 Issue: 8
Author(s): Manlio Tolomeo, Francesco Dieli, Nicola Gebbia and Daniele Simoni
Affiliation:
Keywords: Bcr-Abl, chronic myelogenous leukemia, tyrosine kinase inhibitors
Abstract: Imatinib mesylate (Gleevec) is a drug unique for the treatment of certain forms of cancer. It works by targeting, and turning off, specific tyrosine kinase proteins that cause the uncontrolled cell growth and the inhibition of apoptosis in cancer cells. Imatinib was designed on the basis of the structure of the ATP binding site of the Abl protein kinase with the aim to stabilize the inactive form of Bcr-Abl, an oncoprotein involved in malignant transformation in chronic myelogenous leukemia (CML). However, imatinib can also target other tyrosine kinase proteins different from Bcr-Abl such as Kit, that is the suspected cause of gastrointestinal stromal tumor (GIST). Despite successful clinical results observed in the last years, the long-term effects of imatinib and its ability to completely eradicate CML are still unknown. Moreover, similar to many other anti-cancer drugs, clinical resistance to imatinib has emerged. In this review we will discuss the in vitro and in vivo results obtained with the novel tyrosine kinase inhibitors developed to overcome imatinib resistance in Bcr-Abl expressing hematologiocal disorders.
Export Options
About this article
Cite this article as:
Tolomeo Manlio, Dieli Francesco, Gebbia Nicola and Simoni Daniele, Tyrosine Kinase Inhibitors for the Treatment of Chronic Myeloid Leukemia, Anti-Cancer Agents in Medicinal Chemistry 2009; 9 (8) . https://dx.doi.org/10.2174/187152009789124637
DOI https://dx.doi.org/10.2174/187152009789124637 |
Print ISSN 1871-5206 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5992 |
Call for Papers in Thematic Issues
Induction of cell death in cancer cells by modulating telomerase activity using small molecule drugs
Telomeres are distinctive but short stretches present at the corners of chromosomes and aid in stabilizing chromosomal makeup. Resynthesis of telomeres supported by the activity of reverse transcriptase ribonucleoprotein complex telomerase. There is no any telomerase activity in human somatic cells, but the stem cells and germ cells undergone telomerase ...read more
Role of natural compounds as anti anti-cancer agents
Cancer is considered the leading cause of worldwide mortality, accounting for nearly 10 million deaths in 2022. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy remains an important approach in treatment o f several types of cancers, even though ...read more
Signaling and enzymatic modulators in cancer treatment
Cancer accounts for nearly 10 million deaths in 2022 and is considered the leading cause of worldwide mortality. Cancer outcome can be improved through an appropriate screening and early detection and through an efficient clinical treatment. Chemotherapy, radiotherapy and surgery are the most important approach for the treatment of several ...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
Related Articles
-
Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes
Current Gene Therapy Glycogen Synthase Kinase 3 as an Anticancer Drug Target: Novel Experimental Findings and Trends in the Design of Inhibitors
Current Pharmaceutical Design Induced Pluripotent Stem Cells (iPSCs) Derived from Different Cell Sources and their Potential for Regenerative and Personalized Medicine
Current Molecular Medicine Targeting Cancer Stem Cells with Repurposed Drugs to Improve Current Therapies
Recent Patents on Anti-Cancer Drug Discovery Role of Hsp70 in Cancer Growth and Survival
Protein & Peptide Letters Microscopies at the Nanoscale for Nano-Scale Drug Delivery Systems
Current Drug Targets Random Mutagenesis Methods for In Vitro Directed Enzyme Evolution
Current Protein & Peptide Science Influence of Aldo-keto Reductase 1C3 in Prostate Cancer - A Mini Review
Current Cancer Drug Targets Targeting Regulatory T Cells for Anticancer Therapy
Mini-Reviews in Medicinal Chemistry The PI3K Pathway at the Crossroads of Cancer and the Immune System: Strategies for Next Generation Immunotherapy Combinations
Current Cancer Drug Targets Curcumin: the Yellow Molecule with Pleiotropic Biological Effects
Letters in Drug Design & Discovery Azoles as Effective Antifungal Agents: Trends, Scope and Relevance
The Natural Products Journal Genomics and Proteomics of Nucleoside Transporters
Current Pharmacogenomics Ceramidases in Hematological Malignancies: Senseless or Neglected Target?
Anti-Cancer Agents in Medicinal Chemistry Targeting Cancer Cells by an Oxidant-Based Therapy
Current Molecular Pharmacology Plasmid-Mediated Muscle-Targeted Gene Therapy for Circulating Therapeutic Protein Replacement: A Tale of the Tortoise and the Hare?
Current Gene Therapy Advances in Stem Cell Therapy for Leukemia
Current Stem Cell Research & Therapy Anthraquinones: Analytical Techniques as a Novel Tool to Investigate on the Triggering of Biological Targets
Current Drug Targets The Possible Involvement of Glycogen Synthase Kinase-3 (GSK-3) in Diabetes, Cancer and Central Nervous System Diseases
Current Pharmaceutical Design Increased Paternal Age and Child Health and Development
Current Pediatric Reviews