Breast Cancer Chemosensitivity

by Yu, Dihua; Hung, Mien-Chie

• ISBN13: 9780387740379
• ISBN10: 0387740376
• Edition: 1st
• Format: Hardcover
• Copyright: 2007-09-01
• Publisher: Landes Bioscience

Summary

In Breast Cancer Chemosensitivity, a group of world leading experts review critical aspects of resistance to systemic therapy in breast cancer patients. Beginning with a clinical overview of the problem Breast Cancer Chemosensitivity moves on to focus on the latest findings of molecular mechanisms of drug resistance. These include in-depth discussions on multidrug resistance by P-glycoprotein and the multidrug resistance protein family, resistance to therapeutic agent-induced apoptosis, cell cycle deregulation, deregulation of DNA repair, loss of tumor suppressor genes, integrin-mediated adhesion, insulin-like growth factors, epidermal growth factor, and ErbB2 in modulating breast cancer response to systemic therapy, especially, certain chemotherapeutic agents. Mechanisms of resistance to hormonal therapy are also discussed. Breast Cancer Chemosensitivity provides an example of using novel approaches for chemosensitization of breast cancer cells that gives readers an idea about the future direction in breast cancer treatment.

Table of Contents

Overview of Resistance to Systemic Therapy in Patients with Breast Cancer	p. 1
Resistance to Systemic Therapy	p. 3
Mechanisms of Resistance for Agents Used to Treat Breast Cancer	p. 9
Aromatase Inhibitors, Antiestrogens, and Progestins	p. 15
Chemotherapy Sensitivity and Resistance Assays	p. 16
Conclusions and Future Directions	p. 16
Roles of Multidrug Resistance Genes in Breast Cancer Chemoresistance	p. 23
Introduction	p. 23
General Descriptions of MDR1/Pgp, MRP1, and BRCP	p. 25
Roles of Pgp, MRP1, and BCRP in Breast Cancer Chemotherapy	p. 27
Conclusion	p. 28
Therapy-Induced Apoptosis in Primary Tumors	p. 31
Introduction	p. 31
Current Approaches to Target Apoptosis	p. 33
Targeting Core Apoptotic Pathway Components	p. 37
Summary and Conclusions	p. 43
Cell Cycle Deregulation in Breast Cancer: Insurmountable Chemoresistance or Achilles' Heel?	p. 52
Introduction	p. 52
Conventional Chemotherapies of Breast Cancer	p. 54
Folate Antagonists	p. 55
The Cell Cycle as a Therapeutic Target in Breast Cancer	p. 56
Summary	p. 61
p53, BRCA1 and Breast Cancer Chemoresistance	p. 70
p53	p. 72
BRCA1	p. 74
BRCA1 in Sporadic Breast Cancer	p. 77
BRCA1 and Response to Therapy	p. 78
p53 and BRCA1	p. 80
Screening Mutations via Yeast Experiments	p. 81
Summary and Future Questions	p. 81
Integrin-Mediated Adhesion: Tipping the Balance Between Chemosensitivity and Chemoresistance	p. 87
The Integrin Family of Cell Adhesion Receptors	p. 87
Integrins and Cell Proliferation	p. 88
Integrins and Apoptosis	p. 89
Integrins and Cancer	p. 90
Integrin-Mediated Drug Resistance	p. 91
Integrins and Chemoresistance in Breast Cancer	p. 92
The Tumor Microenvironment and Breast Cancer	p. 93
Conclusions	p. 94
Insulin-Like Growth Factors and Breast Cancer Therapy	p. 101
Introduction	p. 101
The IGF System	p. 102
IGFs and Normal Mammary Tissue	p. 103
IGF and Breast Cancer	p. 103
Conventional Chemotherapy for Breast Cancer	p. 104
IGF Signaling Confers Resistance to Chemotherapy	p. 105
IGF-IR and DNA Repair	p. 105
Effects of Breast Cancer Therapy on the IGF System	p. 105
Anti-IGF Strategies in Breast Cancer	p. 106
Combination of Anti-IGF Strategy with Chemotherapy	p. 107
Conclusion	p. 108
EGF Receptor in Breast Cancer Chemoresistance	p. 113
Introduction	p. 113
EGFR Signal Transduction	p. 113
A Central Role for Akt in Chemoresistance	p. 114
EGFR as a Target for Therapy in Chemoresistant Tumors	p. 115
Conclusions and Future Directions	p. 116
Molecular Mechanisms of ERBB2-Mediated Breast Cancer Chemoresistance	p. 119
Introduction	p. 119
ErbB2 and Chemoresistance	p. 120
The Existing Controversy	p. 121
Molecular Mechanisms of ErbB2-Mediated Chemoresistance	p. 121
Targeting ErbB2 to Overcome Chemoresistance	p. 122
Future Investigation	p. 124
Estrogen Receptors in Resistance to Hormone Therapy	p. 130
Introduction	p. 130
Receptor Structure and Function	p. 131
Does Estrogen Receptors a or b Expression Predict Response to Therapy?	p. 132
Mechanisms of Resistance to Hormonal Therapies	p. 132
Future Directions	p. 136
Novel Approaches for Chemosensitization of Breast Cancer Cells: The E1A Story	p. 144
Introduction	p. 144
Mechanisms of Apoptosis: Intrinsic versus Extrinsic Apoptotic Pathways	p. 145
Factors and Key Molecules Involved in the Regulation of Apoptosis and Drug Response in Breast Cancer	p. 146
Structures, Biochemical Features, and Associated Cellular Proteins of E1A	p. 149
Chemosensitization by E1a	p. 150
Conclusion	p. 161
Index	p. 171
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