Clinically Relevant Resistance in Cancer Chemotherapy

390 Pages·2002·12.51 MB·English

by  Alison J. Davis

CLINICALLY RELEVANT
RESISTANCE IN CANCER
CHEMOTHERAPY
Cancer Treatment and Research
Steven T. Rosen, M.D., Series Editor
Goldstein, L.J., Ozols, R. F. (eds.): Anticancer Drug Resistance. Advance.' in Molecular and Clinical
Research. 1994. ISBN 0-7923-2836-1.
Hong, W.K., Weber, R.S. (eds.): Head and Neck Cancer. Basic and Clinical Aspects. 1994.
ISBN 0-7923-3015-3.
Thall, P.F. (ed): Recent Advances in Clinical Trial Design and Analysis. 1995. ISBN 0-7923-3235-0.
Buckner, C. D. (ed): Technical and Biological Components of Marrow Transplantation. 1995. ISBN 0-
7923-3394-2.
Winter, J.N. (ed.): Blood Stem Cell Transplantation. 1997. ISBN 0-7923-4260-7.
Muggia, F.M. (ed): Concepts, Mechanisms. and New Targetsfor Chemotherapy. 1995.
ISBN 0-7923-3525-2.
K1astersky, J. (ed): Infectious Complications of Cancer. 1995. ISBN 0-7923-3598-8.
Kurzrock, R., Talpaz, M. (eds): Cytokines: Interleukins and Their Receptors. 1995. ISBN 0-7923-3636-4.
Sugarbaker, P. (ed): Peritoneal Carcinomatosis: Drugs and Diseases. 1995. ISBN 0-7923-3726-3.
Sugarbaker, P. (ed): Peritoneal Carcinomatosis: Principles ofM anagement. 1995.
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Dickson, R.B., Lippman, M.E. (eds.): Mammary Tumor Cell Cycle. Differentiation and Metastasis.
1995. ISBN 0-7923-3905-3.
Freireich, E.J, Kantarjian, H. (eds.): Molecular Genetics and Therapy of Leukemia. 1995.
ISBN 0-7923-3912-6.
Cabanillas, F., Rodriguez, M.A. (eds.): Advances in Lymphoma Research. 1996. ISBN 0-7923-3929-0.
Miller, A.B. (ed.): Advances in Cancer Screening. 1996. ISBN 0-7923-4019-1.
Hait, W.N. (ed.): Drug Resistance. 1996. ISBN 0-7923-4022-1.
Pienta, K.J. (ed.): Diagnosis and Treatment of Genitourinary Malignancies. 1996. ISBN 0-7923-4164-3.
Arnold, A.J. (ed.): Endocrine Neoplasms. 1997. ISBN 0-7923-4354-9.
Pollock, R.E. (ed.): Surgical Oncology. 1997. ISBN 0-7923-9900-5.
Verweij, J., Pinedo, H.M., Suit, H.D. (eds.): Soft Tissue Sarcomas: Present Achievements and Future
Prospects. 1997. ISBN 0-7923-9913-7.
Walterhouse, D.O., Cohn, S. L. (eds.): Diagnostic and Therapeutic Advances in Pediatric Oncology.
1997. ISBN 0-7923-9978-1.
Mittal, B.B., Purdy, J.A., Ang, K.K. (eds.): Radiation Therapy. 1998. ISBN 0-7923-9981-1.
Foon, K.A., Muss, H.B. (eds.): Biological and Hormonal Therapies of Cancer. 1998. ISBN 0-7923-9997-8.
Ozols, R.F. (ed.): Gynecologic Oncology. 1998. ISBN 0-7923-8070-3.
Noskin, G. A. (ed.): Management of Infectious Complications in Cancer Patients. 1998. ISBN 0-7923-
8150-5
Bennett, e. L. (ed.): Cancer Policy. 1998. ISBN 0-7923-8203-X
Benson, A. B. (ed.): Gastrointestinal Oncology. 1998. ISBN 0-7923-8205-6
Tallman, M.S. , Gordon, L.t. (eds.): Diagnostic and Therapeutic Advances in HematologiC Malignancies.
1998. ISBN 0-7923-8206-4
von Gunten, e.F. (ed.): Palliative Care and Rehabilitation of Cancer Patients. 1999. ISBN 0-7923-8525-X
Burt, R.K., Brush, M.M. (eds): Advances in Allogeneic Hematopoietic Stem Cell Transplantation. 1999.
ISBN 0-7923-7714-1
Angelos, P. (ed): Ethical Issues in Cancer Patient Care 2000. ISBN 0-7923-7726-5
Gradishar, W.J., Wood, W.e. (eds): Advances in Breast Cancer Management. 2000. ISBN 0-7923-7890-3
Sparano, Joseph A. (ed.): HIV & HTLV-l Associated Malignancies. 2001. ISBN 0-7923-7220-4.
Ettinger, David S. (ed.): Thoracic Oncology. 2001. ISBN 0-7923-7248-4.
Bergan, Raymond e. (ed.): Cancer Chemoprevention. 2001. ISBN 0-7923-7259-X.
Raza, A., Mundie, S.D. (eds): Myelodysplastic Syndromes & Secondary Acute Myelogenous Leukemia 2001.
ISBN: 0-7923-7396.
Talamonti, Mark S. (ed): Liver Directed Therapyfor Primary and Metastatic Liver Tumors. 2001.
ISBN 0-7923-7523-8.
Stack, M.S., Fishman, D.A. (eds): Ovarian Cancer. 200 I. ISBN 0-7923-7530-0.
Bashey, A., Ball, E.D. (eds): Non-Myeloablative Allogeneic Transplantation. 2002. ISBN 0-7923-7646-3
Leong, Stanley P.L. (ed.): Atlas of Selective Sentinel Lymphadenectomy for Melanoma. Breast Cancer and
Colon Cancer. 2002. ISBN 1-4020-7013-6
Andersson, B., Murray D., (eds.): Clinically Relevant Resistance in Cuncer Chemotherapy. 2002.
ISBN 1-4020-7200-7
CLINICALL Y RELEVANT
RESISTANCE IN CANCER
CHEMOTHERAPY
edited by
Borje Andersson, M.D., Ph.D.
MD Anderson Cancer Center
Houston, Texas, USA.
and
David Murray, Ph.D.
Cross Cancer Institute
Edmonton, Alberta, Canada.
SPRINGER SCIENCE+BUSINESS MEDIA, LLC
ISBN 978-1-4613-5428-4 ISBN 978-1-4615-1173-1 (eBook)
DOI 10.1007/978-1-4615-1173-1
Library of Congress Cataloging-in-Publication Data
A C.I.P. Catalogue record for this book is available
from the Library of Congress.
Copyright © 2002 by Springer Science+Business Media New York
Originally published by Kluwer Academic Publishers in 2002
Softcover reprint ofthe hardcover Ist edition 2002
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TABLE OF CONTENTS
-----------------------------------------------------------------------xv
List of contributors
------------------------------------------------------------------------------------XIX
Preface
Chapter 1
Tumor physiology and resistance to chemotherapy: repopulation
and drug penetration. Alison J. Davis and Ian F. Tannock
1. Introduction ---------------------------------------------------------------------------1
2. Repopulation -------------------------------------------------------------------------2
2.1 Cell kinetic factors affecting response to chemotherapy ---------------2
2.2 Repopulation and radiation therapy-----------------------------------------3
2.3 RepopUlation and chemotherapy --------------------------------------------5
2.4 Models of repopulation between cycles of chemotherapy--------------7
2.5 Potential methods for inhibition of repopulation following
chemotherapy -------------------------------------------------------------------9
3. Drug penetration through tissue ------------------------------------------------ 11
3.1 Methods for study of drug penetration ----------------------------------- 11
3.2 Penetration of tissue by anticancer drugs -------------------------------- 13
3.3 Factors that influence penetration of drugs through tissue ----------- 16
3.4 Factors that might influence drug penetration -------------------------- 19
Chapter 2
The role of membrane transporters in cellular resistance to
anticancer nucleoside drugs. Marilyn L. Clarke, John R. Mackey,
Stephen A. Baldwin, James D. Young and Carol E. Cass
1. Introduction ------------------------------------------------------------------------- 27
2. Nucleoside transport processes ------------------------------------------------ 28
2.1 Characterized ENT processes ---------------------------------------------- 28
2.2 The es transporter (hENT!) ------------------------------------------------ 29
2.3 The ei transporter (hENT2)------------------------------------------------- 29
2.4 The hENT3 transporter ------------------------------------------------------ 31
2.5 Characterized CNT processes---------------------------------------------- 31
2.6 The cit transporter (hCNT! )------------------------------------------------ 32
2.7 The elft ransporter (hCNT2 )------------------------------------------------ 33
2.8 The eib transporter (hCNT3)----------------------------------------------- 34
2.9 Concentrative nucleoside transport processes mediated by
unknown proteins------------------------------------------------------------- 34
VI
3. The role of nucleoside transport in anticancer nucleoside activity
and cellular resistance --------------------------------------------------------- 35
3.1 Transport processes and cytotoxicity ------------------------------------- 35
3.2 Transporter-mediated mechanisms of drug resistance ---------------- 35
3.2.1 Resistance to nucleoside analogs in cultured cancer
cell lines ----------------------------------------------------------- 36
3.3 Clinical evidence for transport-related resistance to
nucleoside analogs ---------------------------------------------------------- 37
3 .3 .1 Cytarab ine------------------------------------------------------------- 37
3.3.2 Fludarabine ------------------------------------------------------------ 38
3.3.3 Cladribine ----------------------------------------------------------- 39
3.3.4 Gemcitabine -------------------------------------------------------- 39
3.3.5 Capecitabine ------------------------------------------------------- 40
3.4 Measuring nucleoside drug uptake as a resistance marker---------- 41
Chapter 3
MDR and MRP gene families as cellular detenninant factors for
resistance to clinical anticancer agents. Lei Deng, Shigaru Patebe,
Yen-Chiu Lin-Lee, Toshihisa Ishikawa and M. Tien Kuo
1. Introduction ------------------------------------------------------------------- 49
2. MDR --------------------------------------------------------------------------- 51
2.1 Biology of the MDR system ---------------------------------------------- 51
2.2 Regulation of MDR gene expression and P-glycoprotein
activity ------------------------------------------------------------------- 51
2.3 Clinical relevance ofMDRI in cancer chemotherapy --------------- 52
2.3.1 Significance ofMDRI expression in hematological
neop lasms ------------------------------------------------------------- 52
2.3.2 Significance ofMDRI expression in solid tumors------------- 53
2.3.3 Clinical trials using P-glycoprotein reversal agents----------- 54
3. Multidrug resistance-associated protein (MRP) ----------------------------- 56
3.1 The biology of MRP ------------------------------------------------------- 56
3.2 Regulation of MRP function --------------------------------------------- 57
3.3.1 Clinical relevance ofMRP in cancer chemotherapy----------- 58
Chapter 4
The glutathione system in alkylator resistance. David Hamilton,
Nasser Fotouhi-Ardakani and Gerald Batist
1. Introduction ------------------------------------------------------------------------- 67
2. The glutathione system ---------------------------------------------------------- 68
2.1 Glutathione biosynthesis -------------------------------------------------- 68
2.2 'Y-Glutamylcysteine synthetase and glutathione synthetase ---------- 69
VII
2.3 Glutathione-S-transferases-------------------------------------------------- 71
2.4 GS-X pumplMRP ------------------------------------------------------------ 72
3. The glutathione system in cancer and chemoresistance-------------------- 72
3 .1 G ST s --------------------------------------------------------------------------- 73
3.2 y-GCS and GSH -------------------------------------------------------------- 74
3.3 GS-X pump -------------------------------------------------------------------- 75
4. Manipulation of the glutathione system in cancer treatment-------------- 76
4.1 Buthionine sulfoximine (BSO) -------------------------------------------- 76
4.2 OTZ ----------------------------------------------------------------------------- 78
4.3 0 ltipraz ------------------------------------------------------------------------ 79
4.4 Ethacrynic acid---------------------------------------------------------------- 79
4.5 Other GSH system modulators -------------------------------------------- 80
Chapter 5
The role of signal transduction pathways in drug and radiation
resistance. Steven Grant, Paul B. Fisher and Paul Dent
1. The mitogen activated protein kinase (MAPK) pathway ------------------ 89
2. The C-Jun NH -terminal kinase (JNK)/stress activated protein
2
kinase (SAPK) pathway --------------------------------------------------------- 91
3. An overview of the role of the MAPK pathway in proliferation,
differentiation and survival signaling------------------------------------------ 93
4. An overview of the role of the JNK pathway in proliferation,
differentiation and apoptotic signaling --------------------------------------- 95
5. Potential direct roles for MAPK and JNK signaling in the control
of the cell cycle and DNA repair following irradiation and drug
exposure --------------------------------------------------------------------------- 96
6. MAPK signaling --------------------------------------------------------------- 97
7. JNK signaling ---------------------------------------------------------------------- 99
Chapter 6
Mechanisms of repair ofinterstrand crosslinks in DNA.
Randy J. Legerski and Christopher Richie
1. Introduction ------------------------------------------------------------------------109
2. Repair of ICLs in E. coli -------------------------------------------------------110
3. Recombination in eucaryotes--------------------------------------------------112
4. Mediators of recombination ---------------------------------------------------113
5. Processing of interstrand crosslinks in DNA --------------------------------119
VIII
Chapter 7
DNA repair in resistance to bifunctional alkylating and
platinating agents. David Murray
1. Introduction ------------------------------------------------------------------------J2 9
2. DNA repair pathways-----------------------------------------------------------J3 0
2.1 The NER pathway -----------------------------------------------------------J3 0
2.2 The repair of interstrand cross links --------------------------------------J 3 J
AG T - --------------------------------------------------------------------------1 32
2.3
2.4 Mismatch repair (MMR)---------------------------------------------------J3 2
2.5 The base excision repair (BER) pathway -------------------------------J 32
3. Direct measurement of the repair of DNA lesions in genomic
DNA following treatment of tumor cells with anticancer agents -------J 33
3.1 Cisplatin -----------------------------------------------------------------------J3 3
3.2 Melphalan ---------------------------------------------------------------------J3 4
3.3 Cyclophosphamide analogs -----------------------------------------------J3 4
3.4 Gene-specific repair---------------------------------------------------------J 35
3.5 Caveats ------------------------------------------------------------------------J 3 5
4. Surrogate assays where an exogenous DNA sequence is
damaged and reactivated by a host (tumor) cell----------------------------J3 6
4.1 UV- irradiated virus or plasmid probes for NER ----------------------J 36
4.2 Reactivation or repair of DNA probes treated with cisplatin -------138
4.3 HCR of DNA probes treated with other agents that induce
ISCs ----------------------------------------------------------------------------139
5. Levels of DNA repair gene transcripts or proteins in tumor cells-------140
5.1 Cisplatin -----------------------------------------------------------------------J 4 J
5.2 Melphalan and mechlorethamine----------------------------------------J 42
5.3 Cyclophosphamide and its analogs --------------------------------------J 43
5.4 Chemotherapeutic nitrosoureas -------------------------------------------144
5.5 Caveats ------------------------------------------------------------------------J 44
6. Mismatch repair-------------------------------------------------------------------14 5
7. A G T --------------------------------------------------------------------------------J4 5
8. DNA damage tolerance mechanisms in drug resistance ------------------J 46
9. DNA repair inhibition -----------------------------------------------------------J 47
10. DNA repair genes for bone marrow cytoprotection -----------------------148
Chapter 8
Leukemic cell insensitivity to cyclophosphamide and other
oxazapbospborines mediated by aldebyde debydrogenase(s).
Norman E. Sladek
I. Introduction -----------------------------------------------------------------------J 6 J
IX
2. General mechanisms of cellular insensitivity to
oxazaphosphorines ---------------------------------------------------------------163
3. Specific involvement of aldehyde dehydrogenase in cellular
insensitivity to oxazaphosphorines--------------------------------------------166
Chapter 9
Mechanisms of resistance against cyclophosphamide and
ifosfamide: can they be overcome without sacrificing selectivity?
Susan M. Ludeman and Michael P. Gamcsik
1. Introduction ------------------------------------------------------------------------177
2. The metabolism of CP and IF --------------------------------------------------179
2.1 Aldehyde dehydrogenase (ALDH)---------------------------------------179
2.2 C4-substituted CP/IF and analogs of AP/AIF --------------------------181
2.3 Stereochemistry --------------------------------------------------------------J8 2
2.4 Analogs of PM and IPM ---------------------------------------------------183
3. Glutathione and its associated enzymes --------------------------------------185
3.1 Methods of circumventing glutathione-mediated resistance --------186
4. DNA repair ------------------------------------------------------------------------188
5. PM and IPM -----------------------------------------------------------------------189
6. AGT and acrolein-----------------------------------------------------------------191
Chapter 10
Cellular mechanisms of cyclophosphamide resistance: model
studies in human medulloblastoma cell lines. Henry S. Friedman,
Stewart P. Johnson and o. Michael Colvin
I. Cyclophosphamide therapy of medulloblastoma---------------------------199
2. Cyclophosphamide metabolism------------------------------------------------200
3. Medulloblastoma cell lines as a model for this tumor---------------------201
4. Mechanisms of cyclophosphamide resistance ------------------------------201
5. Cyclophosphamide resistance in human medulloblastoma cell
lines ---------------------------------------------------------------------------------202
5 .1 ALD H --------------------------------------------------------------------------203
5.2 GSH and GST ----------------------------------------------------------------204
5.3 Repair of 4HC-induced DNA interstrand crosslinks -----------------206
6. Quantitation of ONA interstrand crosslink repair--------------------------206
Chapter 11
Model studies of cyclophosphamide resistance in human myeloid
leukemia. Borje S. Andersson and David Murray
1. Resistance to cyclophosphamide analogs in cancer treatment-----------211
2. The role of ALDH in resistance to oxazaphosphorines -------------------212
x
3. The role ofnon-ALDH mechanisms in resistance to
oxazaphosphorines ---------------------------------------------------------------213
4. A human myeloid leukemia model for oxazaphosphorine
resistance --------------------------------------------------------------------------215
5. Phenotypic/biochemical characterization of the B5-1803 CML
cell line ----------------------------------------------------------------------------216
5.1 Biological characteristics; clonogenic survival------------------------216
5.2 Stability of the B5-1803 phenotype -------------------------------------216
5.3 Cross-resistance to other DNA-damaging agents ---------------------217
5.4 Aldehyde dehydrogenase -------------------------------------------------218
5.5 GST protein activity and GSH levels------------------------------------220
5.6 DNA damage and repair --------------------------------------------------221
5.7 Cell cycle checkpoint activation-----------------------------------------222
6. Genetic characterization of B5-1803 cells -----------------------------------223
6.1 Cytogenetics ----------------------------------------------------------------223
6.2 General approaches to the assessment of altered gene
expression in drug-resistant cells -----------------------------------------225
6.3 Atlas 7742-1 :h uman cancer cDNA arrays------------------------------225
6.4 Atlas 7850-1 :human 1.2 I cDNA arrays -------------------------------226
6.5 Differential display of mRNA --------------------------------------------228
6.6 Caveats ----------------------------------------------------------------------228
7. Apoptosis--------------------------------------------------------------------------229
8. Clinically-relevant low-degree resistance to oxazaphosphorines
in CML --------------------------------------------------------------------------231
Chapter 12
Mechanisms of drug resistance in AML. Michael Andreeff and
Marina Konopleva
1. Introduction ----------------------------------------------------------------237
2. Cytokines and cytokinetic resistance ----------------------------------------238
2.1 Priming effects ofHGF in AML: cytokinetic resistance ------------240
2.2 Angiogenic Growth Factors in AML-----------------------------------241
2.3 Chemokines in AML -----------------------------------------------------242
3. Leukemic/stromal cell interactions in AML --------------------------------243
4 . .S tem cells in AML -------------------------------------------------------------243
4.1 NOD/scid model: a novel functional stem cell phenotype ----------243
5. Surface antigens as therapeutic targets in AML----------------------------243
5.1 Antibody-targeted therapy for AML-----------------------------------245
6. Multidrug resistance in AML -------------------------------------------------246
6.1 MDR 1------------------------------------------------------------------------246
6.2 MDR modulators ---------------------------------------------------------249