Novel anticancer agents: strategies for discovery and clinical testing
Gespeichert in:
Format: | Buch |
---|---|
Sprache: | English |
Veröffentlicht: |
Amsterdam [u.a.]
Academic Press
2006
|
Schlagworte: | |
Online-Zugang: | Publisher description Inhaltsverzeichnis |
Beschreibung: | Includes bibliographical references and index |
Beschreibung: | xv, 437 p., [20] p. of plates Ill., graph. Darst. 26 cm |
ISBN: | 0120885611 9780120885619 |
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245 | 1 | 0 | |a Novel anticancer agents |b strategies for discovery and clinical testing |c editors, Alex A. Adjei, John K. Buolamwini |
264 | 1 | |a Amsterdam [u.a.] |b Academic Press |c 2006 | |
300 | |a xv, 437 p., [20] p. of plates |b Ill., graph. Darst. |c 26 cm | ||
336 | |b txt |2 rdacontent | ||
337 | |b n |2 rdamedia | ||
338 | |b nc |2 rdacarrier | ||
500 | |a Includes bibliographical references and index | ||
650 | 4 | |a Anticancéreux - Développement | |
650 | 4 | |a Anticancéreux - Essais | |
650 | 4 | |a Antineoplastic agents |x Development | |
650 | 4 | |a Antineoplastic agents |x Testing | |
650 | 4 | |a Antineoplastic Agents | |
650 | 4 | |a Drug Therapy | |
650 | 4 | |a Research |x methods | |
650 | 4 | |a Drug Screening Assays, Antitumor | |
650 | 4 | |a Clinical Trials |x methods | |
650 | 4 | |a Pharmacogenetics | |
700 | 1 | |a Adjei, Alex A. |e Sonstige |4 oth | |
700 | 1 | |a Buolamwini, John K. |e Sonstige |4 oth | |
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adam_text | ¦¦CONTENTS
CONTRIBUTORS XI
PREFACE XV
¦¦ STRATEGIES FOR DRUG DISCOVERY
I A Survey of Novel Molecular Targets for
Anticancer Drug Discovery
JOHN K. BUOLAMWINI
I. Introduction 1
II. Overview of Growth Factor Induced Mitogenic Signaling 3
III. Protein Kinases and Phosphatases 4
IV. Adapter Proteins 12
V. GTP Binding Proteins 12
VI. Oncogenic Transcription Factors 13
VII. Apoptosis, Cell Survival, and Life Span Targets 15
VIII. Angiogenesis and Metastasis Molecular Factors 17
IX. Protein Degradation and Chaperoning Targets 19
X. Chromatin Remodeling Factors 19
XI. Conclusion 20
References 20
I
VI CONTENTS
2 Microarrays: Small Spots Produce Major Advances
in Pharmacogenomics
M.NEES.W. KUSNEZOW.AND C. D. WOODWORTH
I. Introduction to Microarrays 38
II. Advantages of DNA Microarrays 44
III. Major DNA Array Formats: Something for Everyone 45
IV. What is the Best Way to Interface with Microarrays? 52
V. Microarrays and Pharmacogenomics: Revolutionizing Discovery of New
Drugs and Gene Function 55
VI. What Can Go Wrong in cDNA Microarray Experimentation? 65
VII. Array Based Proteomics: How to Investigate Protein Complexity 68
VIII. Emerging Microarray Technologies for High Throughput Proteome
Investigation: A Technical Overview 68
DC. Current and Future Applications of Protein Arrays in Drug Discovery 71
X. How to Deal with all that Data 73
XI. The Future is Only Going to Get Better 74
References 76
3 Strategies to Target Chemotherapeutics to Tumors
CHARLES E ALBRIGHT AND PEARL S. HUANG
I. Background and Rationale 83
II. Antibody Directed Enzyme Prodrug Technique 84
III. Passive Tumor Targeting 84
IV. Targeting by Binding to Tumor Cell Surface Molecules 85
V. Enzyme Activated Targeting 85
VI. Summary and Future Directions 90
References 90
4 QSAR and Pharmacophore Mapping Strategies
in Novel Anticancer Drug Discovery
JAMES J.KAMINSKI
I. Introduction 93
II. Pharmacophore Definition 94
III. Pharmacophore Validation 99
IV. Conclusions 104
References 104
5 Applications of Nuclear Magnetic Resonance and Mass
Spectrometry to Anticancer Drug Discovery
ROBERT POWERS AND MARSHALL M.SIEGEL
I. Introduction 107
II. NMR in Anticancer Drug Discovery 109
III. Mass Spectrometry in Anticancer Drug Discovery 140
CONTENTS VII
IV. MS/NMR Screening Assay 162
V. Conclusions 172
Acknowledgements 172
References 173
6 Antisense Strategies for the Development
of Novel Cancer Therapeutics
RUIWEN ZHANG AND HUIWANG
I. Introduction 191
II. Design and Evaluation of Antisence Oligonucleotides 193
III. Conclusion 202
Acknowledgements 203
References 203
7 Antibodies and Vaccines as Novel Cancer Therapeutics
SVETOMIR N.MARKOVICAND ESTEBAN CELIS
I. Introduction 207
II. Anti Tumor Antibodies 207
III. Cancer Vaccines 212
IV. Conclusion 218
References 219
8 Inhibitors of Apoptosis as Targets for Cancer Therapy
M.SAEED SHEIKH AND YING HUANG
I. The Inhibitors of Apoptosis 223
II. Concluding Remarks 229
References 230
9 Preclinical Testing and Validation
of Novel Anticancer Agents
LLOYD R. KELLAND
I. Introduction 233
II. Target Validation 234
III. A Generic Cascade for Anticancer Drug Discovery 235
IV. High Throughput Cell Free Screens for Activity Against the Target 237
V. In Vitro Cell Line Models 238
VI. In Vivo Testing of Novel Compounds 240
VII. Cassette Dosing 240
VIII. Pharmaceutical Considerations 241
IX. High Throughput In Vivo Anti Tumor Testing: The Hollow Fiber
Assay 241
X. Human Tumor Xenografts 242
XI. Orthotopic, Transgenic, and Other Animal Models 243
I
VIII CONTENTS
XII. Pharmacodynamics 244
XIII. Summary 245
Acknowledgements 245
References 245
¦ !¦ METHODS FOR CLINICAL TESTING OF NOVEL AGENTS
10 Surrogate End Points and Biomarkers for Early Trials
of Novel Anticancer Agents
ALEXA.ADJEI
I. Introduction 249
II. What are Targeted Agents? 250
III. Surrogate Markers or Biomarkers? 250
IV. Biomarkers as Indicators of Drug Effect In Vivo 252
V. Biomarkers as Predictive Factors 252
VI. Biomarkers as Prognostic Factors 253
VII. Technical Issues in the Evaluation of Drug Effects In Vivo 254
VIII. Lessons for the Future 261
Acknowledgements 261
References 261
I I Regulatory Considerations in Clinical Trials
of Novel Anticancer Drugs
GRANT WILLIAMS AND RICHARD PAZDUR
I. Introduction 263
II. Overview of Cancer Drug Regulation 264
III. Regulatory Considerations in Early Cancer Drug Development 267
IV. Regulatory Considerations in Late Drug Development 271
V. Conclusion 283
Acknowledgements 283
References 283
12 Improving the Efficacy and Safety of Anticancer
Agents—The Role of Pharmacogenetics
MARGARET MARY AMEYAW AND HOWARD LMCLEOD
I. Introduction 286
II. Thiopurine Methyltransferase 286
III. DPD 288
IV. Thymidylate Synthase 289
V. ABC Family of Drug Transporters 291
CONTENTS IX
VI. UDP Glucuronosyltransferase IAI Pharmacogenetics and Irinotecan 292
VII. MTHFR Reductase Pharmacogenetics 293
VIII. Cytochrome P4503A Pharmacogenetics 293
IX. Conclusion 293
Acknowledgements 294
References 294
13 Imaging of Pharmacodynamic End Points
in Clinical Trials
ERIC O. ABOAGYE, A. R. PADHANI, AND PATRICIA M. PRICE
I. Introduction 300
II. PET 300
III. Evaluation of Cancer Therapeutics with PET 302
IV. MRI Assessment of Microvessel Function 311
V. Conclusions 328
References 328
14 Devising Proof of Concept Strategies
in Oncology Clinical Trials
PAULS.WISSEL
I. Introduction 337
II. Proof of Concept 338
III. Elements of The Concept 339
IV. Application of Surrogate End Points in Proof of Concept Decision
Making 343
V. Selected Statistical Considerations in Proof of Concept Studies 349
VI. Pharmacodynamic Proof of Concept End Points 352
VII. Pharmacokinetic Proof of Concept End Points 356
VIII. Proceeding From Proof of Concept Directly to Phase III 359
IX. Guidelines and Summary 360
Acknowledgements 361
References 361
15 Clinical Trial Designs for Cytostatic Agents and Agents
Directed at Novel Molecular Targets
EDWARD L KORN, LARRY V. RUBINSTEIN, SALLY A. HUNSBERGER, JAMES M. PLUDA,
ELIZABETH EISENHAUER.AND SUSAN G. ARBUCK
I. Introduction 366
II. Phase I Dose Finding Trials 366
III. Preliminary Efficacy Trials 372
IV. Definitive Randomized Efficacy Trials 376
V. Conclusions 377
References 377
I
X CONTENTS
16 Cancer Gene Therapy Clinical Trials: From the Bench
to the Clinic
EVANTHIA GALANIS
I. Regulatory Requirements and Good Manufacturing Practices for Gene
Transfer Products 381
II. Preclinical Development of Gene Therapy Vectors/Toxicology Testing 382
III. Federal and Institutional Approval Processes for Clinical Gene Therapy
Trials 383
IV. Gene Therapy Clinical Trial Design 384
V. Correlative End Points 386
References 389
17 Molecular Targets for Radiosensitization
ROGER OVE AND JAMES A. BONNER
I. Introduction 391
II. Growth Factor Receptors 394
III. Ras 399
IV. Modulation of p53 401
V. DNA Damage Recognition and Repair 402
VI. Other Promising Approaches 405
VII. Conclusions 407
VIII. Addendum 407
Addendum References 409
References 409
18 Patient Accrual to Clinical Trials
SUSAN QUELLA
I. Introduction 415
II. Setting Up the Environment 415
References 425
Index 427
|
adam_txt |
¦¦CONTENTS
CONTRIBUTORS XI
PREFACE XV
¦¦ STRATEGIES FOR DRUG DISCOVERY
I A Survey of Novel Molecular Targets for
Anticancer Drug Discovery
JOHN K. BUOLAMWINI
I. Introduction 1
II. Overview of Growth Factor Induced Mitogenic Signaling 3
III. Protein Kinases and Phosphatases 4
IV. Adapter Proteins 12
V. GTP Binding Proteins 12
VI. Oncogenic Transcription Factors 13
VII. Apoptosis, Cell Survival, and Life Span Targets 15
VIII. Angiogenesis and Metastasis Molecular Factors 17
IX. Protein Degradation and Chaperoning Targets 19
X. Chromatin Remodeling Factors 19
XI. Conclusion 20
References 20
I
VI CONTENTS
2 Microarrays: Small Spots Produce Major Advances
in Pharmacogenomics
M.NEES.W. KUSNEZOW.AND C. D. WOODWORTH
I. Introduction to Microarrays 38
II. Advantages of DNA Microarrays 44
III. Major DNA Array Formats: Something for Everyone 45
IV. What is the Best Way to Interface with Microarrays? 52
V. Microarrays and Pharmacogenomics: Revolutionizing Discovery of New
Drugs and Gene Function 55
VI. What Can Go Wrong in cDNA Microarray Experimentation? 65
VII. Array Based Proteomics: How to Investigate Protein Complexity 68
VIII. Emerging Microarray Technologies for High Throughput Proteome
Investigation: A Technical Overview 68
DC. Current and Future Applications of Protein Arrays in Drug Discovery 71
X. How to Deal with all that Data 73
XI. The Future is Only Going to Get Better 74
References 76
3 Strategies to Target Chemotherapeutics to Tumors
CHARLES E ALBRIGHT AND PEARL S. HUANG
I. Background and Rationale 83
II. Antibody Directed Enzyme Prodrug Technique 84
III. Passive Tumor Targeting 84
IV. Targeting by Binding to Tumor Cell Surface Molecules 85
V. Enzyme Activated Targeting 85
VI. Summary and Future Directions 90
References 90
4 QSAR and Pharmacophore Mapping Strategies
in Novel Anticancer Drug Discovery
JAMES J.KAMINSKI
I. Introduction 93
II. Pharmacophore Definition 94
III. Pharmacophore Validation 99
IV. Conclusions 104
References 104
5 Applications of Nuclear Magnetic Resonance and Mass
Spectrometry to Anticancer Drug Discovery
ROBERT POWERS AND MARSHALL M.SIEGEL
I. Introduction 107
II. NMR in Anticancer Drug Discovery 109
III. Mass Spectrometry in Anticancer Drug Discovery 140
CONTENTS VII
IV. MS/NMR Screening Assay 162
V. Conclusions 172
Acknowledgements 172
References 173
6 Antisense Strategies for the Development
of Novel Cancer Therapeutics
RUIWEN ZHANG AND HUIWANG
I. Introduction 191
II. Design and Evaluation of Antisence Oligonucleotides 193
III. Conclusion 202
Acknowledgements 203
References 203
7 Antibodies and Vaccines as Novel Cancer Therapeutics
SVETOMIR N.MARKOVICAND ESTEBAN CELIS
I. Introduction 207
II. Anti Tumor Antibodies 207
III. Cancer Vaccines 212
IV. Conclusion 218
References 219
8 Inhibitors of Apoptosis as Targets for Cancer Therapy
M.SAEED SHEIKH AND YING HUANG
I. The Inhibitors of Apoptosis 223
II. Concluding Remarks 229
References 230
9 Preclinical Testing and Validation
of Novel Anticancer Agents
LLOYD R. KELLAND
I. Introduction 233
II. Target Validation 234
III. A Generic Cascade for Anticancer Drug Discovery 235
IV. High Throughput Cell Free Screens for Activity Against the Target 237
V. In Vitro Cell Line Models 238
VI. In Vivo Testing of Novel Compounds 240
VII. Cassette Dosing 240
VIII. Pharmaceutical Considerations 241
IX. High Throughput In Vivo Anti Tumor Testing: The Hollow Fiber
Assay 241
X. Human Tumor Xenografts 242
XI. Orthotopic, Transgenic, and Other Animal Models 243
I
VIII CONTENTS
XII. Pharmacodynamics 244
XIII. Summary 245
Acknowledgements 245
References 245
¦ !¦ METHODS FOR CLINICAL TESTING OF NOVEL AGENTS
10 Surrogate End Points and Biomarkers for Early Trials
of Novel Anticancer Agents
ALEXA.ADJEI
I. Introduction 249
II. What are Targeted Agents? 250
III. Surrogate Markers or Biomarkers? 250
IV. Biomarkers as Indicators of Drug Effect In Vivo 252
V. Biomarkers as Predictive Factors 252
VI. Biomarkers as Prognostic Factors 253
VII. Technical Issues in the Evaluation of Drug Effects In Vivo 254
VIII. Lessons for the Future 261
Acknowledgements 261
References 261
I I Regulatory Considerations in Clinical Trials
of Novel Anticancer Drugs
GRANT WILLIAMS AND RICHARD PAZDUR
I. Introduction 263
II. Overview of Cancer Drug Regulation 264
III. Regulatory Considerations in Early Cancer Drug Development 267
IV. Regulatory Considerations in Late Drug Development 271
V. Conclusion 283
Acknowledgements 283
References 283
12 Improving the Efficacy and Safety of Anticancer
Agents—The Role of Pharmacogenetics
MARGARET MARY AMEYAW AND HOWARD LMCLEOD
I. Introduction 286
II. Thiopurine Methyltransferase 286
III. DPD 288
IV. Thymidylate Synthase 289
V. ABC Family of Drug Transporters 291
CONTENTS IX
VI. UDP Glucuronosyltransferase IAI Pharmacogenetics and Irinotecan 292
VII. MTHFR Reductase Pharmacogenetics 293
VIII. Cytochrome P4503A Pharmacogenetics 293
IX. Conclusion 293
Acknowledgements 294
References 294
13 Imaging of Pharmacodynamic End Points
in Clinical Trials
ERIC O. ABOAGYE, A. R. PADHANI, AND PATRICIA M. PRICE
I. Introduction 300
II. PET 300
III. Evaluation of Cancer Therapeutics with PET 302
IV. MRI Assessment of Microvessel Function 311
V. Conclusions 328
References 328
14 Devising Proof of Concept Strategies
in Oncology Clinical Trials
PAULS.WISSEL
I. Introduction 337
II. Proof of Concept 338
III. Elements of "The Concept" 339
IV. Application of Surrogate End Points in Proof of Concept Decision
Making 343
V. Selected Statistical Considerations in Proof of Concept Studies 349
VI. Pharmacodynamic Proof of Concept End Points 352
VII. Pharmacokinetic Proof of Concept End Points 356
VIII. Proceeding From Proof of Concept Directly to Phase III 359
IX. Guidelines and Summary 360
Acknowledgements 361
References 361
15 Clinical Trial Designs for Cytostatic Agents and Agents
Directed at Novel Molecular Targets
EDWARD L KORN, LARRY V. RUBINSTEIN, SALLY A. HUNSBERGER, JAMES M. PLUDA,
ELIZABETH EISENHAUER.AND SUSAN G. ARBUCK
I. Introduction 366
II. Phase I Dose Finding Trials 366
III. Preliminary Efficacy Trials 372
IV. Definitive Randomized Efficacy Trials 376
V. Conclusions 377
References 377
I
X CONTENTS
16 Cancer Gene Therapy Clinical Trials: From the Bench
to the Clinic
EVANTHIA GALANIS
I. Regulatory Requirements and Good Manufacturing Practices for Gene
Transfer Products 381
II. Preclinical Development of Gene Therapy Vectors/Toxicology Testing 382
III. Federal and Institutional Approval Processes for Clinical Gene Therapy
Trials 383
IV. Gene Therapy Clinical Trial Design 384
V. Correlative End Points 386
References 389
17 Molecular Targets for Radiosensitization
ROGER OVE AND JAMES A. BONNER
I. Introduction 391
II. Growth Factor Receptors 394
III. Ras 399
IV. Modulation of p53 401
V. DNA Damage Recognition and Repair 402
VI. Other Promising Approaches 405
VII. Conclusions 407
VIII. Addendum 407
Addendum References 409
References 409
18 Patient Accrual to Clinical Trials
SUSAN QUELLA
I. Introduction 415
II. Setting Up the Environment 415
References 425
Index 427 |
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language | English |
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spelling | Novel anticancer agents strategies for discovery and clinical testing editors, Alex A. Adjei, John K. Buolamwini Amsterdam [u.a.] Academic Press 2006 xv, 437 p., [20] p. of plates Ill., graph. Darst. 26 cm txt rdacontent n rdamedia nc rdacarrier Includes bibliographical references and index Anticancéreux - Développement Anticancéreux - Essais Antineoplastic agents Development Antineoplastic agents Testing Antineoplastic Agents Drug Therapy Research methods Drug Screening Assays, Antitumor Clinical Trials methods Pharmacogenetics Adjei, Alex A. Sonstige oth Buolamwini, John K. Sonstige oth http://www.loc.gov/catdir/enhancements/fy0632/2006272967-d.html Publisher description HBZ Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014770618&sequence=000006&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis |
spellingShingle | Novel anticancer agents strategies for discovery and clinical testing Anticancéreux - Développement Anticancéreux - Essais Antineoplastic agents Development Antineoplastic agents Testing Antineoplastic Agents Drug Therapy Research methods Drug Screening Assays, Antitumor Clinical Trials methods Pharmacogenetics |
title | Novel anticancer agents strategies for discovery and clinical testing |
title_auth | Novel anticancer agents strategies for discovery and clinical testing |
title_exact_search | Novel anticancer agents strategies for discovery and clinical testing |
title_exact_search_txtP | Novel anticancer agents strategies for discovery and clinical testing |
title_full | Novel anticancer agents strategies for discovery and clinical testing editors, Alex A. Adjei, John K. Buolamwini |
title_fullStr | Novel anticancer agents strategies for discovery and clinical testing editors, Alex A. Adjei, John K. Buolamwini |
title_full_unstemmed | Novel anticancer agents strategies for discovery and clinical testing editors, Alex A. Adjei, John K. Buolamwini |
title_short | Novel anticancer agents |
title_sort | novel anticancer agents strategies for discovery and clinical testing |
title_sub | strategies for discovery and clinical testing |
topic | Anticancéreux - Développement Anticancéreux - Essais Antineoplastic agents Development Antineoplastic agents Testing Antineoplastic Agents Drug Therapy Research methods Drug Screening Assays, Antitumor Clinical Trials methods Pharmacogenetics |
topic_facet | Anticancéreux - Développement Anticancéreux - Essais Antineoplastic agents Development Antineoplastic agents Testing Antineoplastic Agents Drug Therapy Research methods Drug Screening Assays, Antitumor Clinical Trials methods Pharmacogenetics |
url | http://www.loc.gov/catdir/enhancements/fy0632/2006272967-d.html http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=014770618&sequence=000006&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
work_keys_str_mv | AT adjeialexa novelanticanceragentsstrategiesfordiscoveryandclinicaltesting AT buolamwinijohnk novelanticanceragentsstrategiesfordiscoveryandclinicaltesting |