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Cancer Drug Resistance: Overviews and Methods

Tác giả: Rueff, José; Rodrigues, António Sebastião

Chủ đề:

Chủ đề: Medicine; Cancer

Nhà xuất bản: Humana Press

Năm xuất bản: 2016

Loại tài liệu: Book

Mô tả vật lý: 318 p.

Định danh: 978-1-4939-3347-1

Ngôn ngữ: en

Đọc trực tuyến

This volume discusses the latest advancements and technologies used in cancer drug resistance research. Cancer Drug Resistance: Overviews and Methods contains chapters that cover topics such as: studying the mechanics of resistance to DNA damaging therapeutic drugs; studies to delineate the role of efflux transporters; expression of drug transporters; resistance to targeted therapies in breast cancer; the role of microRNAs in current pancreatic cancer treatment; and cancer exosomes as mediators of drug resistance or clinical and molecular methods in drug development and the use of bioinformatics in the management of cancer drug resistance data. Written in the highly successful Methods in Molecular Biology series format, chapters include overviews of the main issues in cancer drug resistance and the respective mechanisms, as well as introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cancer Drug Resistance: Overviews and Methods, is a valuable resource to researchers, oncobiologists and clinical oncologists or anyone else who is interested in the study of cancer and its drug resistances.

Cover
Title page
Copyright â Springer Science+Business Media New York 2016
Preface
- References
Contents
Contributors
1 Cancer Drug Resistance: A Brief Overview from a Genetic Viewpoint
- 1 Innate or Intrinsic and Acquired Resistance: Definitions and Mechanisms
- 2 Intrinsic Resistance
  - 2.1 Intrinsic Resistance, Clinical Expertise, and Clinical Guidelines
  - 2.2 Intrinsic Resistance and Pharmacogenetic Patterns
- 3 Acquired Resistance
  - 3.1 Acquired Resistance and Tumor Microưheterogeneity
  - 3.2 Acquired Resistance and Adaptive Compensatory Pathways
- 4 Uptake and Efflux of Drugs Mediated by Transporters: Role in Resistance
- 5 DNA Repair and Cancer Drug Resistance
- 6 Epigenomics and Resistance: The Role of Methylation, Acetylation, and microRNAs
- 7 Tumor Microenvironment and Resistance
- 8 Concluding Remarks
- References
2 Classical and Targeted Anticancer Drugs: An Appraisal of Mechanisms of Multidrug Resistance
- 1 Introduction
- 2 Resistance Involving Altered Drug Pharmacokinetics
- 3 Intrinsic Multidrug Resistance Mechanisms
  - 3.1 Resistance Mediated by P-gp
  - 3.2 Resistance Mediated by Other Transporters
  - 3.3 Pharmacokinetic Consequences of Expression of ABC Transporters
  - 3.4 Use of Inhibitors of ABC Transporters in Combination Chemotherapy
  - 3.5 Multidrug Resistance Mechanisms not Mediated by ABC Transporters
- 4 Resistance Involving Altered Tumor Cytokinetics
  - 4.1 Resistance Arising from an Increased Rate of Tumor Cell Proliferation
  - 4.2 Resistance to Apoptosis
  - 4.3 Resistance Because of Loss of Host Immunity Mechanisms
  - 4.4 Tumor Tissue Heterogeneity and Resistance
- 5 General Protocols for Studying Resistance to Multiple Anticancer Drugs
  - 5.1 Assessment of TransportưMediated Multidrug Resistance
  - 5.2 Assessment of Drug Resistance of Cultured Tumor Cells
  - 5.3 Transplanted Tumors in Animals
  - 5.4 Contribution of Host Immune Mechanisms in Individual Human Tumors
- 6 Conclusions
- References
3 In Vitro Methods for Studying the Mechanisms of Resistance to DNA-Damaging Therapeutic Drugs
- 1 Introduction
- 2 Materials
  - 2.1 Chemicals, Buffers, and Equipment to Be Used in Comet Assay
  - 2.2 Chemicals, Buffers, and Equipment to Be Used in γ-H2AX Immunofluorescent Staining
  - 2.3 Chemicals, Buffers, and Equipment to Be Used for Clonogenic Assay
  - 2.4 Chemicals, Buffers, and Equipment to Be Used in β-Galactosidase Staining
  - 2.5 Chemicals, Buffers to Be Used in Cell Cultures
- 3 Methods
  - 3.1 Measurement of Drug-Induced DNA Breaks Using Comet Assay
    - 3.1.1 Preparation of Cell Cultures and DNAưDamaging Treatment
    - 3.1.2 Slide Preparation
    - 3.1.3 Lysis
    - 3.1.4 Alkaline Treatment
    - 3.1.5 Electrophoresis
    - 3.1.6 Neutralization
    - 3.1.7 DAPI Staining
    - 3.1.8 Analysis
  - 3.2 Measuring DNA Damage Using γ-H2AX Immunofluorescent Staining
    - 3.2.1 Preparation of Cell Cultures and DNAưDamaging Treatment
    - 3.2.2 Fixation, Permeabilization, and Blocking
    - 3.2.3 Immunostaining
    - 3.2.4 Counterstaining and Mounting
    - 3.2.5 Imaging and Image Analysis
  - 3.3 Clonogenic Cell Survival Assay
    - 3.3.1 Plating
    - 3.3.2 Treatment with DNAưDamaging Agents
    - 3.3.3 Fixation and Staining
    - 3.3.4 Colony Counting and Assay Analysis
  - 3.4 SenescenceưAssociated β-Galactosidase Staining
    - 3.4.1 Cell Culture and DNA-Damaging Treatment
    - 3.4.2 Fixation and SA-βưGalactosidase Staining of Cultured Cells
- 4 Notes
- References
4 In Vitro Approaches to Study Regulation of Hepatic Cytochrome P450 (CYP) 3A Expression by Paclitaxel and Rifampicin
- 1 Introduction
- 2 Materials
  - 2.1 Primary Mouse Hepatocyte Isolation and Treatment
  - 2.2 Reverse Transcription-Polymerase Chain Reaction Analysis
    - 2.2.1 RNA Isolation
    - 2.2.2 cDNA Synthesis
    - 2.2.3 Real-Time PCR
  - 2.3 HepG2 Cell Transfection and Treatment
  - 2.4 Luciferase Assay
- 3 Methods
  - 3.1 Isolation of Primary Mouse Hepatocytes
  - 3.2 Hepatocyte Culture and Treatment
  - 3.3 Assessment of Induction of Cyp3a11 by Paclitaxel by Real-Time PCR Analysis
    - 3.3.1 RNA Isolation
    - 3.3.2 cDNA Synthesis
    - 3.3.3 RTPCR
  - 3.4 Transient Transfection of HepG2 Cells
  - 3.5 HepG2 Culture and Treatment
  - 3.6 Dual-Luciferase Reporter Assay Protocol
- 4 Notes
- References
5 Uptake and Permeability Studies to Delineate the Role of Efflux Transporters
- 1 Introduction
- 2 Materials
- 3 Methods
  - 3.1 Cellular Drug Accumulation Study
  - 3.2 Permeability Study
- 4 Notes
- References
6 Dynamics of Expression of Drug Transporters: Methods for Appraisal
- 1 Introduction
- 2 Materials
  - 2.1 Cell Lines
  - 2.2 RNA Isolation and cDNA Synthesis
  - 2.3 Quantitative Real-Time PCR
- 3 Methods
  - 3.1 Cell Lines: In Vitro Experimental System
  - 3.2 Cell Lines
  - 3.3 Freezing Cells
  - 3.4 RNA Isolation and cDNA Synthesis
  - 3.5 Quantitative Real-Time PCR
  - 3.6 Data Analysis
  - 3.7 Mutation Analysis
- 4 Notes
- References
7 Fluorimetric Methods for Analysis of Permeability, Drug Transport Kinetics, and Inhibition of the ABCB1 Membrane Transporter
- 1 Introduction
  - 1.1 P-Glycoprotein (P-gp)/ABCB1 Protein
  - 1.2 Natural Compounds as Inhibitors of MDR Transporters
  - 1.3 Monitoring ABCB1-Mediated Drug Transport of Fluorescent Compounds
- 2 Materials
  - 2.1 Cell Culture
  - 2.2 Accumulation Assays
  - 2.3 Cytotoxicity Assays
- 3 Methods
  - 3.1 Preparation of Cell Cultures
  - 3.2 Cytotoxicity Assay
  - 3.3 Assays to Monitor ABCB1-Mediated Drug Transport of Fluorescent Compounds
- 4 Notes
- References
8 Resistance to Targeted Therapies in Breast Cancer
- 1 Introduction
  - 1.1 Estrogen Receptor Inhibition
    - 1.1.1 Ligand Independent ER Activation
    - 1.1.2 Ligand-Dependent/Genomic Action of ER
    - 1.1.3 Overcoming ET Resistance
    - 1.1.4 The Loss or Change of the Target
    - 1.1.5 Deep Sequencing Studies
  - 1.2 Her2 Inhibition
    - 1.2.1 Trastuzumab
    - 1.2.2 Lapatinib
      - Preclinical Data
      - Clinical Trials
        
        Adjuvant
        
        Metastatic Breast Cancer
        
        Neoadjuvant Breast Cancer
    - 1.2.3 Pertuzumab
    - 1.2.4 T-DM1
    - 1.2.5 Neratinib
    - 1.2.6 Afatinib
  - 1.3 Targeted Therapies for Metastatic Breast Cancer
    - 1.3.1 EGFR (Her1) Inhibition
      - Cetuximab
      - Tyrosine Kinase inhibitors
    - 1.3.2 Angiogenesis Inhibition
      - Bevacizumab
        
        Metastatic Breast Cancer
        
        Adjuvant Setting
        
        Neoadjuvant Breast Cancer
      - Tyrosine Kinase Inhibitors
        
        Cediranib
        
        Sorafenib
        
        Sunitinib
    - 1.3.3 PARP Inhibition
      - Iniparib
      - Olaparib
      - Veliparib
    - 1.3.4 Src Inhibition
    - 1.3.5 PI3K/AKT/mTOR Inhibition
    - 1.3.6 RAS/RAF/MEK/ERK/MAPK Inhibition
    - 1.3.7 FGFR Inhibition
    - 1.3.8 Cell Cycle Inhibition via CDK4/6
    - 1.3.9 Apoptosis Induction
- 2 Conclusion
- References
9 MicroRNAs and Cancer Drug Resistance
- 1 Introduction
- 2 MicroRNAs in Cancer Drug Resistance
  - 2.1 Drug Metabolism
  - 2.2 Drug Transport
  - 2.3 DNA Repair
  - 2.4 Epithelial to Mesenchymal Transition
  - 2.5 Cancer Stem Cells and Drug Resistance
- References
10 The Role of MicroRNAs in Resistance to Current Pancreatic Cancer Treatment: Translational Studies and Basic Protocols for Extraction and PCR Analysis
- 1 Introduction
  - 1.1 The Role of MicroRNA Role in Cancer
  - 1.2 Current Pancreatic Cancer Treatment Regimens and the Role of miRNAs
  - 1.3 Conventional Chemotherapy
    - 1.3.1 Gemcitabine Monotherapy
    - 1.3.2 Gemcitabine and Nab-Paclitaxel
    - 1.3.3 FOLFIRINOX (5-FU, Leucovorin, Irinotecan, and Oxaliplatin)
  - 1.4 Signal Transduction Targeted Therapy
    - 1.4.1 Anti-EGFR Therapy in PDAC
  - 1.5 Conclusions and Future Perspectives
  - 1.6 Practical Protocol: The Use of miRNAs Analysis in Chemoresistance
- 2 Materials
  - 2.1 MicroRNA Extraction from Serum
  - 2.2 MicroRNA Extraction from FFPE Tissue
  - 2.3 Reverse Transcription and Quantitative Real-Time PCR
  - 2.4 Methods
    - 2.4.1 MicroRNA Extraction from Serum
    - 2.4.2 MicroRNA Extraction from FFPE Tissue
    - 2.4.3 MicroRNA Extraction from Cells
    - 2.4.4 MicroRNA Extraction from Fresh Tissue
    - 2.4.5 Reverse Transcription and Quantitative Real-Time PCR
- 3 Data Analysis
- 4 Notes
- References
11 Methods for Studying MicroRNA Expression and Their Targets in Formalin-Fixed, Paraffin-Embedded (FFPE) Breast Cancer Tissues
- 1 Introduction
- 2 Material
  - 2.1 Total RNA Isolation
  - 2.2 Reverse Transcription and Quantitative Real-Time PCR
  - 2.3 Immunohistochemistry
- 3 Methods
  - 3.1 Total RNA Isolation
    - 3.1.1 Deparaffinization
    - 3.1.2 Protein Digestion
    - 3.1.3 Nucleic Acid Isolation
  - 3.2 Reverse Transcription and Quantitative Real-Time PCR
    - 3.2.1 cDNA Synthesis
    - 3.2.2 Real-Time qPCR (See Note 15)
  - 3.3 Immunohistochemistry
  - 3.4 Data Analysis
- 4 Notes
- References
12 The Regulatory Role of Long Noncoding RNAs in Cancer Drug Resistance
- 1 Introduction
  - 1.1 Mechanisms of Resistance to Cancer Drugs
  - 1.2 Role of lncRNA in Drug Resistance
  - 1.3 Involvement of Stem Cells
    - 1.3.1 Urothelial Carcinoma-Associated 1 (UCA1; Also Known as CUDR)
    - 1.3.2 Long Intergenic ncRNA Regulator of Reprogramming (linc-ROR)
    - 1.3.3 X-Inactive-Specific Transcript (XIST)
  - 1.4 Involvement of EMT/CSC
    - 1.4.1 Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT-1)
  - 1.5 Cell Cycle and Apoptosis
    - 1.5.1 Up-Regulated in Hepatocellular Carcinoma (URHC)
    - 1.5.2 HOX Transcript Antisense RNA (HOTAIR)
    - 1.5.3 Prostate-Specific Transcript (Nonprotein Coding) PCGEM1
    - 1.5.4 Growth Arrest-Specific 5 (GAS5)
    - 1.5.5 AK126698
    - 1.5.6 E2F1-Regulated Inhibitor of Cell Death (ERIC)
    - 1.5.7 P21-Associated ncRNA DNA Damage Activated (PANDA)
    - 1.5.8 p53-Dependent Apoptosis Modulator (PDAM)
    - 1.5.9 HOXA Transcript at the Distal Tip (HOTTIP)
  - 1.6 Drug Transport and Metabolism
    - 1.6.1 Vault Noncoding RNAs
    - 1.6.2 H19
  - 1.7 Drug Resistance-Related Protein
    - 1.7.1 MDR-Related and Up-Regulated lncRNA (MRUL)
    - 1.7.2 Adriamycin Resistance Associated (ARA)
  - 1.8 Secondary Mutation or Translocation
    - 1.8.1 Plasmacytoma Variant Translocation 1 (PVT1)
  - 1.9 Endocrine Resistance
    - 1.9.1 Breast Cancer Anti-estrogen Resistance 4 (BCAR4)
- 2 Conclusion
- References
13 Cancer Exosomes as Mediators of Drug Resistance
- 1 Introduction
  - 1.1 The Tumor Microưenvironment, the Pre-metastatic Niche, and the Role of Tumor Exosomes in Tumor Progression and Metastasis Development
  - 1.2 The Tumor Microenvironment and Chemotherapy Response
- 2 Materials
- 3 Methods
  - 3.1 Exosome Purification from Cell Culture
  - 3.2 Exosome Isolation from Fresh Mouse and Human Plasma
  - 3.3 Exosome Isolation for Retrospective Studies Using Frozen Human Plasma
  - 3.4 Electron Microscope Analysis of Exosomes
  - 3.5 Identification of ExosomeưSpecific Markers by Western Blot Analysis
  - 3.6 Quantification of Exosome Size, Distribution, and Number by LM10 Nanoparticle Characterization System (NanoSight)
- References
14 Isolation and Characterization of Cancer Stem Cells from Primary Head and Neck Squamous Cell Carcinoma Tumors
- 1 Introduction
- 2 Materials
  - 2.1 Tumor Digestion
  - 2.2 Fluorescence-Activated Cell Sorting
  - 2.3 Orosphere Culture
- 3 Methods
  - 3.1 Preparation for Digestion
  - 3.2 Tumor Digestion
  - 3.3 Isolation of Cancer Stem Cells
  - 3.4 Orosphere Assay
- 4 Notes
- References
15 Clinical and Molecular Methods in Drug Development: Neoadjuvant Systemic Therapy in Breast Cancer as a Model
- 1 Introduction
- 2 Materials
  - 2.1 Breast Biopsy
  - 2.2 Diagnostic Pathology Report
  - 2.3 Conventional Radiology
  - 2.4 Axillary Biopsy
  - 2.5 Skin Biopsy
  - 2.6 Magnetic Resonance Imaging
  - 2.7 Positron Emission Tomography
  - 2.8 Multidisciplinary Team
  - 2.10 Tumor Labeling
  - 2.9 NAST
  - 2.11 Biopsy at 2 Weeks
  - 2.12 Clinical Response Assessment
  - 2.13 Radiological Response Assessment
  - 2.14 PET Response Assessment
  - 2.15 Surgery
  - 2.16 Surgical Pathology
  - 2.17 Adjuvant Therapy
  - 2.18 Survival
- 3 Methods
  - 3.1 Breast Biopsy
  - 3.2 Pathology Report
  - 3.3 Conventional Radiology
  - 3.4 Axillary Biopsy
  - 3.5 Skin Biopsy
  - 3.6 MRI
  - 3.7 PET
  - 3.8 MDT
  - 3.9 PST
  - 3.10 Tumor Labeling
  - 3.11 Biopsy at 2 Weeks
  - 3.12 Radiological Response Assessment
  - 3.13 PET Response Assessment
  - 3.14 Clinical Response Assessment
  - 3.15 Surgery
  - 3.16 Surgical Pathology
  - 3.17 RT-qPCR
  - 3.18 Immuno histochemistry
  - 3.19 Adjuvant Systemic Therapy
  - 3.20 Survival
- 4 Notes
- References
16 Proteomics in the Assessment of the Therapeutic Response of Antineoplastic Drugs: Strategies and Practical Applications
- 1 Introduction
  - 1.1 Proteomics Strategies
    - 1.1.1 Discovery Proteomics Approach
  - 1.2 Gold Standards in Discovery Proteomics
  - 1.3 Target Proteomics
    - 1.3.1 Frequently Used Methods in Target-Based Proteomics
  - 1.4 Verification Phase
  - 1.5 Which Proteome to Investigate?
  - 1.6 Mass Spectrometry and Considerations When Starting Proteomics-Based Biomarker Study
  - 1.7 Proteomics in Practice: Chemotherapeutic Response
- 2 Conclusions
- References
17 Managing Drug Resistance in Cancer: Role of Cancer Informatics
- 1 Introduction
  - 1.1 Cancer Drug Resistance
  - 1.2 Cancer Informatics and Management of Drug Resistance
  - 1.3 COSMIC and CCLE
  - 1.4 HerceptinR
  - 1.5 CancerDR
  - 1.6 Alignment/Mutation Module
    - 1.6.1 Total Align
    - 1.6.2 Custom Align
    - 1.6.3 Mutants
    - 1.6.4 Structure Alignment
  - 1.7 Target Structure Module
  - 1.8 Clusters/Groups Module
    - 1.8.1 Clustering of Mutant Drug Target Sequences (Target Cluster)
    - 1.8.2 Clustering of Cancer Cell Lines Assayed on Different Drugs (Cell Line Cluster)
    - 1.8.3 Clustering of Anticancer Drugs for Different Cancer Cell Lines (Drug Cluster)
  - 1.9 Map/Alignment Module
    - 1.9.1 Short Reads
    - 1.9.2 Contigs
    - 1.9.3 Sequences
  - 1.10 Limitations and Future Prospects
- References
Index