Abstract
Acquired drug resistance continues to be one of the major obstacles hindering the successful treatment of many forms of cancer. Compounds utilized as antagonists of these cytoprotective mechanisms have, for the most part, proven to be ineffective at overcoming clinical resistance to cytotoxic drugs. Recently, the tumor cell microenvironment has been found to have a significant bearing on the survival of tumor cells following exposure to a wide variety of anti-neoplastic agents, prior to the acquisition of known drug resistance mechanisms. Specifically, interactions between cell surface integrins and extracellular matrix components have been shown to be responsible for this phenomenon of innate drug resistance, which we have termed Cell Adhesion Mediated Drug Resistance, or CAM-DR. Following its discovery using a multiple myeloma cell line model, evidence for CAM-DR has been found in a multitude of other human tumor cell types. In contrast to many other drug resistance mechanisms, integrin-mediated cell signaling is capable of protecting against death induced by an extremely wide variety of structurally and functionally diverse agents from traditional DNA damaging agents to the promising novel kinase inhibitor STI-571. This review examines the role of integrins in regard to their ability to protect tumor cells from drug- and radiation-induced apoptosis through numerous intracellular mechanisms. Current and future antagonists of specific integrin heterodimers may have the potential to sensitize tumor cells when used in combination with standard chemotherapy regimens. Specific signal transduction pathways initiated by integrin ligation will also be discussed as potential bridge points for inhibiting cell survival during cytotoxic drug exposure.
Keywords: cam-dr, ecm, vcam, chronicmyelogenous leukemia cml, bcr-abl kinase inhibitors, phosphatidyl inositol
Current Cancer Drug Targets
Title: Integrins as Novel Drug Targets for Overcoming Innate Drug Resistance
Volume: 2 Issue: 1
Author(s): Jason S. Damiano
Affiliation:
Keywords: cam-dr, ecm, vcam, chronicmyelogenous leukemia cml, bcr-abl kinase inhibitors, phosphatidyl inositol
Abstract: Acquired drug resistance continues to be one of the major obstacles hindering the successful treatment of many forms of cancer. Compounds utilized as antagonists of these cytoprotective mechanisms have, for the most part, proven to be ineffective at overcoming clinical resistance to cytotoxic drugs. Recently, the tumor cell microenvironment has been found to have a significant bearing on the survival of tumor cells following exposure to a wide variety of anti-neoplastic agents, prior to the acquisition of known drug resistance mechanisms. Specifically, interactions between cell surface integrins and extracellular matrix components have been shown to be responsible for this phenomenon of innate drug resistance, which we have termed Cell Adhesion Mediated Drug Resistance, or CAM-DR. Following its discovery using a multiple myeloma cell line model, evidence for CAM-DR has been found in a multitude of other human tumor cell types. In contrast to many other drug resistance mechanisms, integrin-mediated cell signaling is capable of protecting against death induced by an extremely wide variety of structurally and functionally diverse agents from traditional DNA damaging agents to the promising novel kinase inhibitor STI-571. This review examines the role of integrins in regard to their ability to protect tumor cells from drug- and radiation-induced apoptosis through numerous intracellular mechanisms. Current and future antagonists of specific integrin heterodimers may have the potential to sensitize tumor cells when used in combination with standard chemotherapy regimens. Specific signal transduction pathways initiated by integrin ligation will also be discussed as potential bridge points for inhibiting cell survival during cytotoxic drug exposure.
Export Options
About this article
Cite this article as:
Damiano S. Jason, Integrins as Novel Drug Targets for Overcoming Innate Drug Resistance, Current Cancer Drug Targets 2002; 2 (1) . https://dx.doi.org/10.2174/1568009023334033
DOI https://dx.doi.org/10.2174/1568009023334033 |
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
-
Matrine: Bioactivities and Structural Modifications
Current Topics in Medicinal Chemistry PET Tracers for Mapping Adenosine Receptors as Probes for Diagnosis of CNS Disorders
Central Nervous System Agents in Medicinal Chemistry Targeted Enzyme Prodrug Therapies
Mini-Reviews in Medicinal Chemistry Vascular Biomarkers in Asthma and COPD
Current Topics in Medicinal Chemistry Thalidomide Analogues as Anticancer Drugs
Recent Patents on Anti-Cancer Drug Discovery Amyloid Precursor Protein Processing in Vivo - Insights from a Chemically- Induced Constitutive Overactivation of Protein Kinase C in Guinea Pig Brain
Current Medicinal Chemistry Recent Advances in Delivery Through the Blood-Brain Barrier
Current Topics in Medicinal Chemistry Fiber-Optic Technologies in Laser-Based Therapeutics: Threads for a Cure
Current Pharmaceutical Biotechnology Rho GTPase Activating Proteins in Cancer Phenotypes
Current Protein & Peptide Science Nucleic Acid-Based Therapeutics for Glioblastoma
Anti-Cancer Agents in Medicinal Chemistry Transmembrane Protein 166 and its Significance
Protein & Peptide Letters Targeting EZH2 for Cancer Therapy: Progress and Perspective
Current Protein & Peptide Science Artemisia Species as a New Candidate for Diabetes Therapy: A Comprehensive Review
Current Molecular Medicine Preclinical Development of Novel Anti-Glioma Drugs Targeting the Endoplasmic Reticulum Stress Response
Current Pharmaceutical Design Procarbazine – A Traditional Drug in the Treatment of Malignant Gliomas
Current Medicinal Chemistry Ex Vivo Liver – Directed Gene Therapy for the Treatment of Metabolic Diseases: Advances in Hepatocyte Transplantation and Retroviral Vectors
Current Gene Therapy Small-Molecule Inhibitors of Bcl-2 Family Proteins as Therapeutic Agents in Cancer
Recent Patents on Anti-Cancer Drug Discovery Novel Homeodomain Transcription Factor Nkx2.2 in the Brain Tumor Development
Current Cancer Drug Targets TRP Channels: New Potential Therapeutic Approaches in CNS Neuropathies
CNS & Neurological Disorders - Drug Targets Mechanisms of Tubulin Binding Ligands to Target Cancer Cells: Updates on their Therapeutic Potential and Clinical Trials
Current Cancer Drug Targets