Abstract
Treatment outcomes for chronic myelogenous leukemia (CML) have shown major improvements as a result of the development of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been rarely achieved. CML cells are protected from cytotoxic insults, including those by TKIs, through various collaborative BCR-ABL1- mediated and -independent mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These protective mechanisms include overlapping cell signaling pathways for normal hematopoietic proliferation, modulation of molecules associated with the BCL2 family protein-regulated programmed cell death pathway, autophagic cell protection capability, bone marrow environment-mediated cell protective signaling, abnormally upregulated genetic instability and other BCRABL1- independent kinase activities. To develop a more effective treatment strategy for a cure by means of total leukemic cell killing, a thorough understanding of how CML cells survive and resist cytotoxic insults is essential. In this article, we review current knowledge about multifaceted BCR-ABL1-related and -unrelated mechanisms for survival and death of CML cells and present suggestions for the development of new therapeutic strategies for complete elimination of residual CML cells during TKI treatment.
Keywords: Apoptosis, autophagy, CML, gene instability, microenvironment, stem cell
Current Cancer Drug Targets
Title:Multifaceted Mechanisms for Cell Survival and Drug Targeting in Chronic Myelogenous Leukemia
Volume: 13 Issue: 1
Author(s): J. Kuroda, Y. Shimura, M. Yamamoto-Sugitani, N. Sasaki and M. Taniwaki
Affiliation:
Keywords: Apoptosis, autophagy, CML, gene instability, microenvironment, stem cell
Abstract: Treatment outcomes for chronic myelogenous leukemia (CML) have shown major improvements as a result of the development of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been rarely achieved. CML cells are protected from cytotoxic insults, including those by TKIs, through various collaborative BCR-ABL1- mediated and -independent mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These protective mechanisms include overlapping cell signaling pathways for normal hematopoietic proliferation, modulation of molecules associated with the BCL2 family protein-regulated programmed cell death pathway, autophagic cell protection capability, bone marrow environment-mediated cell protective signaling, abnormally upregulated genetic instability and other BCRABL1- independent kinase activities. To develop a more effective treatment strategy for a cure by means of total leukemic cell killing, a thorough understanding of how CML cells survive and resist cytotoxic insults is essential. In this article, we review current knowledge about multifaceted BCR-ABL1-related and -unrelated mechanisms for survival and death of CML cells and present suggestions for the development of new therapeutic strategies for complete elimination of residual CML cells during TKI treatment.
Export Options
About this article
Cite this article as:
Kuroda J., Shimura Y., Yamamoto-Sugitani M., Sasaki N. and Taniwaki M., Multifaceted Mechanisms for Cell Survival and Drug Targeting in Chronic Myelogenous Leukemia, Current Cancer Drug Targets 2013; 13 (1) . https://dx.doi.org/10.2174/1568009611309010069
DOI https://dx.doi.org/10.2174/1568009611309010069 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...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
-
HLA Peptide-mediated Strategies for Modulation of Cellular and Humoral Immune Response in Transplantation
Current Pharmacogenomics RNA Interference: A New Targeted Tumour Therapy?
Current Cancer Therapy Reviews The Novel Role for Lyn in Integrin Signaling in Human Disease
Current Signal Transduction Therapy HSP90 Inhibitors: Multi-Targeted Antitumor Effects and Novel Combinatorial Therapeutic Approaches in Cancer Therapy
Current Medicinal Chemistry Huntingtons Disease: New Frontiers for Molecular and Cell Therapy
Current Drug Targets Pro-inflammatory Cytokines in Animal and Human Gestation
Current Pharmaceutical Design Recent Progress in Research on Ribosome Inactivating Proteins
Current Protein & Peptide Science Cancer Stem Cells: The ‘Achilles Heel’ of Chemo-Resistant Tumors
Recent Patents on Anti-Cancer Drug Discovery Management of Early Stage Chronic Myeloid Leukemia: State-of-the-art Approach and Future Perspectives
Current Cancer Drug Targets New Indications for Established Drugs: Combined Tumor-Stroma-Targeted Cancer Therapy with PPARγ Agonists, COX-2 Inhibitors, mTOR Antagonists and Metronomic Chemotherapy
Current Cancer Drug Targets Cyclophilin function in Cancer; lessons from virus replication
Current Molecular Pharmacology Bioactive Chromone Derivatives – Structural Diversity
Current Bioactive Compounds PI3K/Akt Signalling Pathway Specific Inhibitors: A Novel Strategy to Sensitize Cancer Cells to Anti-Cancer Drugs
Current Pharmaceutical Design Bone Metastasis: Molecular Mechanisms Implicated in Tumour Cell Dormancy in Breast and Prostate Cancer
Current Cancer Drug Targets Purine Analogues as Kinase Inhibitors: A Review
Recent Patents on Anti-Cancer Drug Discovery Histone Deacetylase Inhibitors: Molecular and Biological Activity as a Premise to Clinical Application
Current Drug Metabolism Small Interfering RNA for Effective Cancer Therapies
Mini-Reviews in Medicinal Chemistry Targeting of Leukemia-Initiating Cells to Develop Curative Drug Therapies: Straightforward but Nontrivial Concept
Current Cancer Drug Targets The ATP-driven Hsp60 Machinery: Biological and Clinical Implications
Current Immunology Reviews (Discontinued) Editorial: Looking Forward to Another Successful Year
Current Cancer Drug Targets