Abstract
The introduction of concepts proposing multiple cellular subgroups in the normal female breast leads to the hypothesis that distinct cellular phenotypes in the female breast give rise to different subtypes of breast carcinomas e.g. expressing ER, HER2 and EGFR differentially. Therefore, origin of breast carcinoma types may be based on the formation of a cancer prone field in which the committed progenitor cells pass mutations to their progenies, glandular as well as myoepithelial cells. The existence of such field within the human breast was inferred from the results on primary breast cancer obtained by PCR-based microsatellite analysis of allelic imbalance (AI) of the EGF receptor gene. Here, normal breast tissue shows egfr AI adjacent to breast cancer tissue also harboring egfr gene AI. The therapeutic implications of such a model are fundamental, as tumors may display different phenotypes which arise from transformation of different progenitor cells as well as from transformation of more differentiated progenies within a cancer prone field. Thereby they may show up with different clinical courses of the disease, higher rates of metastases and responses to therapy. In this review, we discuss this mechanism focusing on the EGF receptor as an example for regulators of progenitor cell growth in many tissues. Phylloides tumors serve as a putative model for embryonic differentiation stage ruled by EGFR signaling and give insights into the tumor-host-interaction. The inhibition of the EGF receptor by specific monoclonal antibodies (e.g. Erbitux) will give an answer in as far EGFR-signaling is decisive for the development of an invasive breast cancer. For this purpose new models have been inaugurated which vary in the EGF receptor gene dosage and protein expression. Moreover, we discuss the EGF receptor as a target for the treatment of pre-malignant lesions with a high risk for malignant growth, e.g. DCIS, which certainly will be detected more frequently by mammography screening programs soon.
Keywords: Committed progenitor, cancer prone field, egfr, AI, amplification, CA-SSR I
Current Cancer Drug Targets
Title: Allelic Imbalances of the egfr Gene as Key Events in Breast Cancer Progression – the Concept of Committed Progenitor Cells
Volume: 8 Issue: 5
Author(s): K. Agelopoulos, H. Buerger and B. Brandt
Affiliation:
Keywords: Committed progenitor, cancer prone field, egfr, AI, amplification, CA-SSR I
Abstract: The introduction of concepts proposing multiple cellular subgroups in the normal female breast leads to the hypothesis that distinct cellular phenotypes in the female breast give rise to different subtypes of breast carcinomas e.g. expressing ER, HER2 and EGFR differentially. Therefore, origin of breast carcinoma types may be based on the formation of a cancer prone field in which the committed progenitor cells pass mutations to their progenies, glandular as well as myoepithelial cells. The existence of such field within the human breast was inferred from the results on primary breast cancer obtained by PCR-based microsatellite analysis of allelic imbalance (AI) of the EGF receptor gene. Here, normal breast tissue shows egfr AI adjacent to breast cancer tissue also harboring egfr gene AI. The therapeutic implications of such a model are fundamental, as tumors may display different phenotypes which arise from transformation of different progenitor cells as well as from transformation of more differentiated progenies within a cancer prone field. Thereby they may show up with different clinical courses of the disease, higher rates of metastases and responses to therapy. In this review, we discuss this mechanism focusing on the EGF receptor as an example for regulators of progenitor cell growth in many tissues. Phylloides tumors serve as a putative model for embryonic differentiation stage ruled by EGFR signaling and give insights into the tumor-host-interaction. The inhibition of the EGF receptor by specific monoclonal antibodies (e.g. Erbitux) will give an answer in as far EGFR-signaling is decisive for the development of an invasive breast cancer. For this purpose new models have been inaugurated which vary in the EGF receptor gene dosage and protein expression. Moreover, we discuss the EGF receptor as a target for the treatment of pre-malignant lesions with a high risk for malignant growth, e.g. DCIS, which certainly will be detected more frequently by mammography screening programs soon.
Export Options
About this article
Cite this article as:
Agelopoulos K., Buerger H. and Brandt B., Allelic Imbalances of the egfr Gene as Key Events in Breast Cancer Progression – the Concept of Committed Progenitor Cells, Current Cancer Drug Targets 2008; 8 (5) . https://dx.doi.org/10.2174/156800908785133213
DOI https://dx.doi.org/10.2174/156800908785133213 |
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
Innovative Cancer Drug Targets: A New Horizon in Oncology
Cancer remains one of the most challenging diseases, with its complexity and adaptability necessitating continuous research efforts into more effective and targeted therapeutic approaches. Recent years have witnessed significant progress in understanding the molecular and genetic basis of cancer, leading to the identification of novel drug targets. These include, but ...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
-
Perspectives on Medicinal Properties of Benzoquinone Compounds
Mini-Reviews in Medicinal Chemistry Regulatory T Cells and Cancer Therapy: An Old Story with a New Hope
Current Cancer Therapy Reviews Monoclonal Antibodies, Small Molecule Inhibitors and Antibody-drug Conjugates as HER2 Inhibitors
Current Medicinal Chemistry Lipids as a Target for Drugs Modulating Multidrug Resistance of Cancer Cells
Current Drug Targets Microbubble-Assisted p53, RB, and p130 Gene Transfer in Combination with Radiation Therapy in Prostate Cancer
Current Gene Therapy A Review of the Possible Mechanisms of Action of Tocotrienol – A Potential Antiosteoporotic Agent
Current Drug Targets Editorial
Current Medicinal Chemistry Nonviral Vectors for Cancer Gene Therapy: Prospects for Integrating Vectors and Combination Therapies
Current Gene Therapy Targeted Drug Delivery Systems for Lung Macrophages
Current Drug Targets Sphingolipid Signaling Pathways as Potential Therapeutic Targets in Gliomas
Mini-Reviews in Medicinal Chemistry Immunological Aspects of Metritis in Dairy Cows: A Review
Endocrine, Metabolic & Immune Disorders - Drug Targets Quassinoids: From Traditional Drugs to New Cancer Therapeutics
Current Medicinal Chemistry Ribozyme- and Deoxyribozyme-Strategies for Medical Applications
Current Drug Targets Controlled Drug Delivery Using Microdevices
Current Pharmaceutical Biotechnology Eradicating the Roots: Advanced Therapeutic Approaches Targeting Breast Cancer Stem Cells
Current Pharmaceutical Design Meet Our Editorial Board Member:
Current Cancer Drug Targets Small-Animal Molecular Imaging for Preclinical Cancer Research: μPET and μSPECT
Current Radiopharmaceuticals MicroRNAs in Human Diseases
Recent Patents on DNA & Gene Sequences In-Gel Protein Phosphatase Assays and Other Useful Methods for the Detection of Protein Phosphatase Activities
Anti-Cancer Agents in Medicinal Chemistry Discovery of Medically Significant Lantibiotics
Current Drug Discovery Technologies