Table of Contents
cover-large.tif
front-matter.pdf
Foreword
Contents
Contributors
fulltext.pdf
1 Multidrug Resistance Mediated by MDR-ABC Transporters
Introduction
Mechanistic Aspects of ABC Transporters
MDR-ABC Transporters
Transported Substrates
Gene Regulation
Significance of MDR-ABC Transporters in Cancer
Association of MDR-ABC Transporters with Treatment Failure
Overcoming MDR with Inhibitors
Emerging Role of MDR-ABC Transporters in Resistance Against Targeted Agents
Conclusion
References
fulltext_2.pdf
2 Metastasis and Drug Resistance
Introduction
The Pathogenesis of Metastasis
Multidrug Resistance
Reversal of Experimental MDR
Calcium Channel Blockers
Verapamil and Other Clinically Approved Agents
Verapamil Derivatives and Other Experimental Calcium Channel Blockers
Calmodulin Antagonists
Antibiotics and Analogs
Indole Alkaloids
Cyclosporins and Analogs
Hormones and Antihormones
Pharmaceutical Emulsifying Surfactants
Liposomal Encapsulation
Other Molecules
Clinical Reversal of MDR
Overview of Experimental MDR-Reversal
Metastasis and Drug Resistance
Tumor Angiogenesis
Antivascular Therapy of MDR Prostate Carcinoma
References
fulltext_3.pdf
3 The Role of Autophagy and Apoptosis in the Drug Resistance of Cancer
Introduction
Role of Autophagy in the Drug Resistance of Cancer
Role of Autophagy in Cancer Treatment
Role of Autophagy in Tumorigenesis
Mechanism Regulating Autophagy and Apoptosis
PI3K-AKT-mTOR Signaling Pathway
BECN1
BCL2 and Adenovirus E1B 19kDa Interaction Protein 3 (BNIP3)
p53 Tumor Suppressor Pathway
ER Stress
Other Pathways
Targeting Autophagy in Drug Resistance of Cancer
Crosstalk Between Autophagy and Apoptosis
Combination Treatment for Drug Resistance
Conclusion
References
fulltext_4.pdf
4 Mechanisms of Resistance to Targeted Tyrosine Kinase Inhibitors
Introduction
Discovery of Viral and Cellular Oncogenes
BCR-ABL Targeted Therapy
The Philadelphia Chromosome
BCR-ABL Signaling in CML
Imatinib
Imatinib Resistance in CML
Nonmutation-Dependent Mechanisms
Mutation of BCR-ABL
Second-Generation BCR-ABL Inhibitors Aimed at Overcoming Imatinib Resistance
Dasatinib
Dasatinib Resistance
Nilotinib
Overcoming T315I Resistance
EGFR-Targeted Therapy
EGFR and Cancer
Gefitinib and Erlotinib: EGFR-Targeted Therapies
Response to Gefitinib Treatment
Erlotinib
Gefitinib and Erlotinib Resistance
Secondary EGFR Mutations
Non-EGFR Mutation-Dependent Mechanisms
Overcoming T790M Resistance
Concluding Remarks
References
fulltext_5.pdf
5 Targeting Transglutaminase-2 to Overcome Chemoresistance in Cancer Cells
Introduction
TG2The Protein with a Split Personality
TG2, Drug Resistance, and Metastasis
TG2-Mediated Cell Signaling
TG2-Mediated NF-B Activation
TG2 Promotes Cell Survival and Chemoresistance
Therapeutic Significance of TG2
Conclusions
References
fulltext_6.pdf
6 Extracellular Matrix-Mediated Drug Resistance
Introduction
ECM Proteins Promote Drug Resistance
Mechanisms of ECM-Mediated Drug Resistance
Altered Drug Penetration
Reduced DNA Damage
Effects on Cell Proliferation
Interaction with Cell-Surface Integrins
Integrin Signalling Pathways and Drug Resistance
The Role of FAK as a Mediator of Drug Resistance
The Role of ILK in Drug Resistance
The Role of PI3-K Signalling in Integrin-Mediated Drug Resistance
ECM-Mediated Drug Resistance in the Context of Metastatic Cancer
Conclusions and Future Directions
References
fulltext_7.pdf
7 Oxidative Stress and Drug Resistance in Cancer
Introduction
Redox Alterations in Cancer
The Findings
Role of Oxidative Stress in Tumorigenesis
Mechanisms of the Intrinsic ROS Stress in Cancer Cells
Adaptive Response to Oxidative Stress
Activation of Redox-Sensitive Transcription Factors
NF-B
Nrf2
c-Jun
HIF-1
Alterations in Regulators of Redox Homeostasis
Alterations in the Function of Proteins Involving in Cell Survival
Mechanisms of Drug Resistance as the Consequence of Redox Adaptation
Enhanced Cell Survival
Increased Capacity to Maintain Redox Homeostasis
Moderate Increase of Oxidative Stress Inhibits Apoptotic Execution
Increased Repair and Tolerance of DNA Damage
Altered Drug Metabolism
Therapeutic Strategy to Overcome Drug Resistance
Targeting Transcription Factors that Regulate Survival Pathways
Targeting the Regulators of Redox Homeostasis
Targeting Redox-Sensitive Factors Involving Cell Survival and Apoptosis
Concluding Remarks
References
fulltext_8.pdf
8 Nuclear Factor-B and Chemoresistance: How Intertwined Are They?
Introduction
What Is NF-B?
NF-B and Cancer
NF-B Regulates the Expression of Cell Proliferative Gene Products
NF-B Regulates the Expression of Anti-apoptotic Gene Products
NF-B Regulates the Expression of Invasive Gene Products
NF-B Regulates the Expression of Genes Involved in Angiogenesis
NF-B Regulates the Expression of Genes Involved in Tumor Cell Metastasis
Chemotherapeutic Agents Activate NF-B and Induce Drug Resistance
NF-B-Mediated Drug Resistance Mechanisms
Multidrug Resistance (MDR) Gene
COX-2
Survivin
Bcl-2/Bcl-xL
Inhibitor of Apoptosis Proteins
cFLIP
Cell Adhesion Molecules
PI3K/Akt
mTOR Pathway
Protein Tyrosine Kinases
5-LOX
EGFR
IL-6
HER-2
PKC/PKA
Cyclin D1
c-Myc
Integrin
TG-2
STAT3
NF-B Inhibitors and Chemosensitization
Conclusion
References
fulltext_9.pdf
9 Drug Resistance and the Tumor Suppressor p53: The Paradox of Wild-Type Genotype in Chemorefractory Cancers
Introduction
Role of p53 in the Response of Sensitive Tumor Cells to Antitumor Agents
Concept of Drug Resistance Caused by p53 Mutation
Mutations in p53 Modulate Drug Response and Specificity
Gene Status of p53 and Clinical Drug Resistance
Relative Resistance Based on p53 Gene Status and the Role of the Antitumor Agent
Resistance Mechanisms in Tumor Cells Harboring Wild-Type p53
Downregulation of DNA Damage Recognition Proteins
Downregulation of Upstream Pathways
ATM/Chk2 and ATM/HIPK2 Pathways
ATR/Chk1 Pathway
Failure to Turn ''on'' the p53 Activation Switch
Downregulation of Promoter Response to p53 in Target Genes
Conclusion
References
fulltext_10.pdf
10 Resistance to Differentiation Therapy
Introduction
Acute Promelocytic Leukemia and Differentiation Therapy
Retinoids and All- trans -Retinoic Acid
The Biologic Effects of Retinoids Are Modulated Through Nuclear Receptors
Pathogenesis of Acute Promyelocytic Leukemia
Molecular Basis of ATRA Therapy in APL
Resistance to Differentiation Therapy
Accelerated ATRA Metabolism
Increased Cellular RA-Binding Proteins (CRABPs)
Mutations at the Ligand-Binding Domain of RAR
Constitutive Degradation of PMLRAR
P-Glycoprotein Expression
Histone Deacetylase (HDAC) Activity
The Role of PML/RAR Isoforms in Resistance
Telemerase Activity
Tissue Transglutaminase Expression
Topoisomerase II Activity
Potential Treatment Strategies to Overcome ATRA Resistance in APL
Liposomal ATRA
Arsenic Trioxide (As 2 O 3 )
Histone Deacetylase Inhibitors
Others
Conclusion
References
fulltext_11.pdf
11 MicroRNAs and Drug Resistance
Introduction
Biogenesis
Cellular Function
MiRNA and Cancer
MiRNAs as Oncogenes and Tumor Suppressors
MiRNA and Drug Resistance
Conclusion
References
fulltext_12.pdf
12 Molecular Signatures of Drug Resistance
Introduction
Microarrays in the Heterogeneity of Cancer
Observational vs. Experimental Studies in Drug Resistance
Microarray Analysis: Supervised, Unsupervised, Significance, and Prediction
Cancer Cell Lines and Signatures of Drug Resistance
Linking Cell Line Data with Human Observational Data
Animal Models and Signatures of Drug Resistance
Linking Mouse Models with Human Cancer Biology
Human Studies and Signatures of Drug Resistance
Future Directions in Molecular Signatures of Drug Resistance
Stem Cells
Microenvironment
Pathways or Modules vs. Individual Genes as Functional Units
Conclusions
References
fulltext_13.pdf
13 Assessment of Drug Resistance in Anticancer Therapy by Nuclear Imaging
Introduction
Use of PET
Imaging with PET
Use of FDG to Identify Patients Resistant to Chemotherapy
Imaging Pharmacokinetic Resistance
Metabolic Resistance
Metabolism of 5-FU and Resistance
Imaging Physiological Causes of Resistance
Blood Flow
Angiogenesis
Hypoxia
Molecular Resistance
Hormone Receptor-Mediated Resistance
Apoptosis
p53 Tumour Suppressor
Imaging Signal Transduction Pathways
Imaging Proliferation
DNA Repair
Integrin Signalling
MDR
Conclusions
References
fulltext_14.pdf
14 Overcoming Drug Resistance by Phytochemicals
Introduction
Cancer Drug Resistance
Phytochemicals
PhytochemicalChemotherapeutic Synergy
Epigallocatechin-3-gallate
Health Effects
Cancer Drug Resistance
Curcumin
Health Effects
Cancer Drug Resistance
Resveratrol
Health Effects
Cancer Drug Resistance
Other Phytochemicals
Quercetin
Genistein
Indole-3-carbinol
Phytochemicals from Medicinal Herbs
Botanical Extracts
Discussion
Antagonistic Effects
Combination Therapy
Multiple Molecular Targets
Safety
Consumer Use of Phytochemicals
Phytochemical Safety
Bioavailability
Bioefficacy
Hormesis
Conclusion and Perspective
References
back-matter.pdf
Index
