Abstract
Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that occur predominantly in the stomach and the small bowel. Their pathogenesis is generally based on primary activating mutations in the KIT or PDGFRα genes that result in constitutive activation of receptor tyrosine kinase activity. Imatinib, first designed to competitively inhibit the ATP-binding pocket of the BCR-ABL tyrosine kinase exhibits inhibition also in the KIT and PDGFRα tyrosine kinases, which revolutionized the therapy of gastrointestinal stromal tumors, a disease without any systemic treatment options prior to imatinib. Clinical benefit is achieved in approximately 85% of patients with unresectable or metastatic disease with a median progression-free survival of 19 to 26 months and an overall survival approaching 5 years. Disease progression results from different mechanisms of resistance most frequently involving the emergence of secondary mutations in KIT exons 13, 14, or 17. Several newer drugs have been studied in patients failing or being intolerant to imatinib, including the multitargeted agent sunitinib as well as other KIT targeting tyrosine kinase inhibitors like nilotinib or agents targeting alternative pathways like anti-angiogenic agents, mTOR-, RAF kinase- and chaperone inhibitors.
Keywords: Gastrointestinal stromal tumour (GIST), molecular targeted therapy, tyrosine kinase inhibitor, imatinib, sunitinib, platelet-derived growth factor receptor-alpha, Denaturing high-pressure liquid chromatography, Nilotinib, Vatalanib, Masitinib mesylate, Motesanib, Everolimus, positron emission tomography, rank-preserving structural failure time
Current Cancer Drug Targets
Title: Molecular Targeted Therapy of Gastrointestinal Stromal Tumors
Volume: 11 Issue: 6
Author(s): P. Reichardt, A. Reichardt and D. Pink
Affiliation:
Keywords: Gastrointestinal stromal tumour (GIST), molecular targeted therapy, tyrosine kinase inhibitor, imatinib, sunitinib, platelet-derived growth factor receptor-alpha, Denaturing high-pressure liquid chromatography, Nilotinib, Vatalanib, Masitinib mesylate, Motesanib, Everolimus, positron emission tomography, rank-preserving structural failure time
Abstract: Gastrointestinal stromal tumors (GIST) are mesenchymal tumors that occur predominantly in the stomach and the small bowel. Their pathogenesis is generally based on primary activating mutations in the KIT or PDGFRα genes that result in constitutive activation of receptor tyrosine kinase activity. Imatinib, first designed to competitively inhibit the ATP-binding pocket of the BCR-ABL tyrosine kinase exhibits inhibition also in the KIT and PDGFRα tyrosine kinases, which revolutionized the therapy of gastrointestinal stromal tumors, a disease without any systemic treatment options prior to imatinib. Clinical benefit is achieved in approximately 85% of patients with unresectable or metastatic disease with a median progression-free survival of 19 to 26 months and an overall survival approaching 5 years. Disease progression results from different mechanisms of resistance most frequently involving the emergence of secondary mutations in KIT exons 13, 14, or 17. Several newer drugs have been studied in patients failing or being intolerant to imatinib, including the multitargeted agent sunitinib as well as other KIT targeting tyrosine kinase inhibitors like nilotinib or agents targeting alternative pathways like anti-angiogenic agents, mTOR-, RAF kinase- and chaperone inhibitors.
Export Options
About this article
Cite this article as:
Reichardt P., Reichardt A. and Pink D., Molecular Targeted Therapy of Gastrointestinal Stromal Tumors, Current Cancer Drug Targets 2011; 11 (6) . https://dx.doi.org/10.2174/156800911796191042
DOI https://dx.doi.org/10.2174/156800911796191042 |
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
-
In Vivo Study on Vertical Transmission of the HIV-1 gag Gene via Mouse Oocytes
Current HIV Research Anticancer Agents: VTA or VDA
Current Bioactive Compounds Evidence for Predominance of CCR5-Using HIV-1 Strains During Highly Active Antiretroviral Therapy
Current HIV Research Molecular and Biological Aspects of the Bovine Immunodeficiency Virus
Current HIV Research Prospects for Plant-Derived Chemopreventive Agents Exhibiting Multiple Mechanisms of Action
Current Medicinal Chemistry - Anti-Cancer Agents Drug-Mediated Targeted Disruption of Multiple Protein Activities Through Functional Inhibition of the Hsp90 Chaperone Complex
Current Medicinal Chemistry Scope of Nanotechnology-based Radiation Therapy and Thermotherapy Methods in Cancer Treatment
Current Cancer Drug Targets Annexin A5 Imaging: An Academic Research – Clinical Trials and Theses
Current Molecular Imaging (Discontinued) New Perspectives in the Pharmacological Potential of Naringin in Medicine
Current Medicinal Chemistry Imatinib Mesylate: Targeted Therapy of Gastrointestinal Stromal Tumor
Current Cancer Therapy Reviews Retroviral Protein Transfer: Falling Apart to Make an Impact
Current Gene Therapy Preface
Current Drug Targets - Infectious Disorders Mitochondrial Tolerance to Drugs and Toxic Agents in Ageing and Disease
Current Drug Targets Effect of SDF-1 α on Endogenous Mobilized and Transplanted Stem Cells in Regeneration after Myocardial Infarction
Current Pharmaceutical Design Proteomic Classification of Breast Cancer
Current Drug Targets Platinum-Based Agents for Individualized Cancer Treatment
Current Molecular Medicine Flavopiridol, the First Cyclin-Dependent Kinase Inhibitor: Recent Advances in Combination Chemotherapy
Mini-Reviews in Medicinal Chemistry Current Strategies for Modulating Lymphangiogenesis Signalling Pathways in Human Disease
Current Medicinal Chemistry Transductional Targeting with Recombinant Adenovirus Vectors
Current Gene Therapy Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones
Current Cancer Drug Targets