Breast Cancer Chemosensitivity

186 Pages·2007·1.287 MB·English

by  Ana Maria Gonzalez-Angulo, Flavia Morales-Vasquez (auth.), Dihua Yu, Mien-Chie Hung (eds.)

Breast Cancer Chemosensitivity
ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY
Editorial Board:
NATHAN BACK, State University of New York at Buffalo
IRUN R. COHEN, The Weizmann Institute of Science
ABEL LAJTHA, N.S. Kline Institute for Psychiatric Research
JOHN D. LAMBRIS, University of Pennsylvania
RODOLFO PAOLETTI, University of Milan
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Volume 608
BREAST CANCER CHEMOSENSITIVITY
Edited by Dihua Yu and Mien-Chie Hung
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Breast Cancer Chemosensitivity
Edited by
Dihua Yu
Department of Surgical Oncology, The University of Texas M.D. Anderson
Cancer Center, Houston, Texas, U.S.A.
Mien-Chie Hung
Department of Molecular and Cellular Oncology, The University of Texas M.D.
Anderson Cancer Center, Houston, Texas, U.S.A.
Springer Science+Business Media, LLC
Landes Bioscience
Springer Science+Business Media, LLC
Landes Bioscience
Copyright '2007 Landes Bioscience and Springer Science+Business Media, LLC
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Breast Cancer Chemosensitivity edited by Dihua Yu and Mien-Chie Hung, Landes Bioscience /
Springer Science+Business Media, LLC dual imprint / Springer series: Advances in Experimental
Medicine and Biology
ISBN: 978-0-387-74037-9
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Library of Congress Cataloging-in-Publication Data
Breast cancer chemosensitivity / edited by Dihua Yu, Mien-Chie Hung.
p. ; cm. -- (Advances in experimental medicine and biology ; v. 608)
Includes bibliographical references and index.
ISBN 978-0-387-74037-9
1. Breast--Cancer--Chemotherapy. 2. Drug resistance in cancer cells. I. Yu,
Dihua. II. Hung, Mien-chie. III. Series.
[DNLM: 1. Breast Neoplasms--drug therapy. 2. Antineoplastic Agents--pharma-
cology. 3. Drug Resistance, Neoplasm--physiology. W1 AD559 v.608 2007 / WP
870 B82325 2007]
RC280.B8B6658 2007
616.99'449061--dc22
2007030520
About the Editor...
DIHUA YU, M.D., Ph.D. is the Nylene Eckles Distinguished Professor in Breast
Cancer Research at the The University of Texas, M.D. Anderson Cancer Center.
She is the Director of the Cancer Biology Program, The University of Texas Gradu-
ate School of Biomedical Sciences in Houston. Dr. Yu(cid:31)s research focuses on mo-
lecular mechanisms of breast cancer initiation, progression, metastasis, and thera-
peutic resistance. Her research interest covers broad areas including receptor tyrosine
kinases and downstream signal transduction, cell cycle deregulation, apoptosis, cell
polarity, angiogenesis, and cancer metastasis. She uses 2-Dimensional and 3-
Dimensional cell culture models, SCID and nude mouse models, transgenic and
knockout mouse models, as well as human tumor samples as research models. She
has over 100 publications, has trained many Ph.D. students in her laboratory, and
has received several awards on research and education excellence at the The Uni-
versity of Texas, M.D. Anderson Cancer Center. She serves on several editorial
boards, including Cancer Research.
v
About the Editor...
DR. MIEN-CHIE HUNG is Professor and Chair for the Department of Mo-
lecular and Cellular Oncology at The University of Texas M.D. Anderson Cancer
Center, Houston, Texas. He received his Ph.D. from Brandeis University in Massa-
chusetts. Currently, he also serves as the Director of the Breast Cancer Basic Re-
search Program and is the Ruth Legett Jones Distinguished Chair. Dr. Hung(cid:31)s labo-
ratory has focused on signaling transduction pathways of tyrosine kinase growth
factor receptors such as EGFR and HER-2/neu; molecular mechanisms of oncogenes,
including transformation and tumorigenesis; and molecular mechanisms of tumor
suppressor gene-mediated anti-tumor activities. His group made a critical break-
through in showing that the transmembrane tyrosine kinase receptor EGFR can bind
to a specific DNA sequence in the nucleus and that it functions as a transcription
factor that can activate genes required for cell proliferation. The other main re-
search in Dr. Hung(cid:31)s laboratory is in the area of cancer gene therapy that includes
development of preclinical gene therapy animal models, including breast, ovarian
and pancreatic cancers; identification of therapeutic genes suitable for cancer gene
therapy; and development of gene delivery systems for cancer gene therapy. In ad-
dition to numerous publications and research endeavors, Dr. Hung became an Aca-
demician of the Academia Sinica in Taiwan in July 2002. Dr. Hung serves as a
founding Editorial Member on Cancer Cell as well as an Associate Editor on Cancer
Research, Clinical Cancer Research, Molecular Cancer Research and Molecular
Carcinogenesis.
vi
PREFACE
Breast cancer is the most common cancer and the second leading cause of can-
cer death in American women. Despite advances in early detection and the improved
understanding of the molecular basis of breast cancer biology, about 30% of pa-
tients with early-stage breast cancer have recurrent disease and need effective sys-
temic treatment. Cytotoxic chemotherapies, hormonal therapies, and immunothera-
peutic agents are used in the adjuvant, neoadjuvant, and metastatic setting. Systemic
agents are generally active at the beginning of therapy in the majority of breast
cancers. However, progression occurs after a variable period of time when resis-
tance to therapy develops. In this book, a group of world leading experts review
critical aspects of resistance to systemic therapy in breast cancer patients. The book
begins with a clinical overview of the problem. The following chapters 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 deregu-
lation, deregulation of DNA repair, loss of tumor suppressor genes, integrin-medi-
ated adhesion, insulin-like growth factors, epidermal growth factor, and ErbB2 in
modulating breast cancer response to systemic therapy, especially certain chemo-
therapeutic agents. Mechanisms of resistance to hormonal therapy are also dis-
cussed. Finally, an example of using novel approaches for chemosensitization of
breast cancer cells is described that gives readers an idea about the future direction
in breast cancer treatment. This book is not an encyclopedia of systemic therapy
resistance, but a handy reference to some of the most important aspects of systemic
therapy resistance which allows those who are interested in breast cancer therapy to
get a jump-start on critical issues in breast cancer therapeutic resistance.
Dihua Yu and Mien-Chie Hung
vii
PARTICIPANTS
Tushar Baran Deb Gabriel N. Hortobagyi
Lombardi Comprehensive Cancer Center Department of Breast Medical Oncology
Georgetown University Medical Center The University of Texas M.D. Anderson
Washington, DC Cancer Center
U.S.A. Houston, Texas
U.S.A.
Robert B. Dickson
Georgetown University Medical Center Mien-Chie Hung
Washington, DC Department of Molecular and Cellular
U.S.A. Oncology
The University of Texas M.D. Anderson
Wafik S. El-Deiry Cancer Center
University of Pennsylvania Houston, Texas
Medical Center U.S.A.
Philadelphia, Pennsylvania
U.S.A. Khandan Keyomarsi
Departments of Surgical Oncology
Suzanne A.W. Fuqua and Experimental Radiation Oncology
Departments of Medicine, Breast Center The University of Texas M.D. Anderson
Molecular and Cellular Biology Cancer Center
Baylor College of Medicine Houston, Texas
U.S.A.
Houston, Texas
U.S.A.
M. Tien Kuo
Department of Molecular Pathology
Ana Maria Gonzalez-Angulo
The University of Texas M.D. Anderson
Department of Breast Medical Oncology
Cancer Center
The University of Texas M.D. Anderson
Houston, Texas
Cancer Center
U.S.A.
Houston, Texas
U.S.A.
Laura Lambert
Departments of Surgical Oncology
Matthew H. Herynk
and Experimental Radiation Oncology
Breast Center
The University of Texas M.D. Anderson
Baylor College of Medicine
Cancer Center
and the Methodist Hospital
Houston, Texas
Houston, Texas
U.S.A.
U.S.A.
ix
x Participants
Yong Liao Dihua Yu
Department of Molecular Department of Surgical Oncology
and Cellular Oncology The University of Texas M.D. Anderson
The University of Texas M.D. Anderson Cancer Center
Cancer Center Houston, Texas
Houston, Texas U.S.A.
U.S.A.
Xianke Zeng
David J. McConkey Department of Pharmacology
Department of Cancer Biology University of Minnesota Cancer Center
The University of Texas M.D. Anderson Minneapolis, Minnesota
Cancer Center U.S.A.
Houston, Texas
U.S.A. Mary M. Zutter
Departments of Pathology
Flavia Morales-Vasquez and Cancer Biology
Department of Breast Medical Oncology Vanderbilt University Medical Center
The University of Texas M.D. Anderson The Vanderbilt Clinic
Cancer Center Nashville, Tennessee
Houston, Texas U.S.A.
U.S.A.
Kimberly A. Scata
University of Pennsylvania
Medical Center
Philadelphia, Pennsylvania
U.S.A.
Ming Tan
Department of Surgical Oncology
The University of Texas M.D. Anderson
Cancer Center
Houston, Texas
U.S.A.
Douglas Yee
Department of Pharmacology
and Medicine
University of Minnesota Cancer Center
Minneapolis, Minnesota
U.S.A.
CONTENTS
1. OVERVIEW OF RESISTANCE TO SYSTEMIC THERAPY
IN PATIENTS WITH BREAST CANCER.........................................1
Ana Maria Gonzalez-Angulo, Flavia Morales-Vasquez and Gabriel N. Hortobagyi
Resistance to Systemic Therapy.........................................................................................3
Mechanisms of Resistance for Agents Used to Treat Breast Cancer ..............................9
Aromatase Inhibitors, Antiestrogens, and Progestins....................................................15
Chemotherapy Sensitivity and Resistance Assays..........................................................16
Conclusions and Future Directions..................................................................................16
2. ROLES OF MULTIDRUG RESISTANCE GENES
IN BREAST CANCER CHEMORESISTANCE ..............................23
M. Tien Kuo
Introduction.......................................................................................................................23
General Descriptions of MDR1/Pgp, MRP1, and BRCP...............................................25
Roles of Pgp, MRP1, and BCRP in Breast Cancer Chemotherapy..............................27
Conclusion..........................................................................................................................28
3. THERAPY-INDUCED APOPTOSIS IN PRIMARY TUMORS...............31
David J. McConkey
Introduction.......................................................................................................................31
Current Approaches to Target Apoptosis........................................................................33
Targeting Core Apoptotic Pathway Components...........................................................37
Summary and Conclusions...............................................................................................43
4. CELL CYCLE DEREGULATION IN BREAST CANCER:
INSURMOUNTABLE CHEMORESISTANCE
OR ACHILLES(cid:31) HEEL?.....................................................................52
Laura Lambert and Khandan Keyomarsi
Introduction.......................................................................................................................52
Conventional Chemotherapies of Breast Cancer...........................................................54
Folate Antagonists.............................................................................................................55
xi