Kurzrock / Markman Targeted Cancer Therapy

1. Auflage 2008
ISBN: 978-1-60327-424-1
Verlag: Humana Press
Format: PDF
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 446 Seiten

Emerging technologies in target identification, drug discovery, molecular markers, and imaging are rapidly changing the face of cancer. This book provides a foundation of knowledge in targeted cancer therapeutics. The treatment of cancer is increasingly being individualized, based on an understanding of underlying biologic mechanisms. Poised to change the landscape in oncology, this volume provides a state-of-the-art overview. It will be valuable to practicing and academic physicians, fellows, residents and students, as well as basic scientists, interested in the cancer field.

Autoren/Hrsg.

Kurzrock, Razelle

Markman, Maurie

Inhaltsverzeichnis

1;Dedication;6
2;Preface;7
3;Contents;8
4;Contributors;10
5;Perspectives: Bench to Bedside and Back;12
5.1;Abstract;12
5.2;1. INTRODUCTION;13
5.3;2. DEVELOPMENT OF ONE OF THE FIRST TARGETED THERAPIES: ALL- TRANS RETINOIC ACID AND THE BEDSIDE TO BENCH PARADIGM;14
5.4;3. A MODEL OF BENCH TO BEDSIDE TARGETED DRUG DEVELOPMENT: THE STORY OF IMATINIB IN PHILADELPHIA- POSITIVE ACUTE LYMPHOBLASTIC LEUKEMIA, CHRONIC MYELOGENOUS LEUKEMIA, AND GASTROINTESTINAL STROMAL TUMORS;16
5.4.1;3.1. Imatinib as a Model for Discovery of Approaches to Overcome Resistance;17
5.4.2;3.2. Mathematical Modeling as a Tool for Discovery;18
5.4.3;3.3. GIST and the Development of Targeted Therapy;19
5.5;4. WHAT IS OLD IS NEW AGAIN: DECITABINE AND THE DAWN OF EPIGENETICS;21
5.6;5. NEW MODEL OF CARCINOGENESIS: CANCER STEM CELL HYPOTHESIS;24
5.7;6. LOOKING FORWARD: THE FUTURE OF TRANSLATIONAL MEDICINE;26
5.8;REFERENCES;26
6;Targeted Therapy in Acute Myelogenous Leukemia;31
6.1;CONTENTS;31
6.2;Abstract;31
6.3;1. INTRODUCTION;31
6.4;2. ATRA AND ATO IN APL;32
6.5;3. AGENTS TARGETING CD33;35
6.5.1;3.1. Lintuzumab;35
6.5.2;3.2. Gemtuzumab Ozogamycin (Mylotarg);35
6.6;4. IODINE-131 ANTI-CD45 ANTIBODY;38
6.7;5. FLT3 INHIBITORS;38
6.8;6. FARNESYL TRANSFERASE INHIBITORS;39
6.9;7. EPIGENETIC THERAPY;40
6.9.1;7.1. Hypomethylating Agents (Azacitidine and Decitabine);40
6.9.2;7.2. Hypomethylating Agents + Histone Deacetylase Inhibitors;44
6.9.3;7.3. Epigenetic-Acting Drugs as Sensitizers to Other Therapies;44
6.9.4;7.4. Antagonists of BCL-2 and MDR1;45
6.9.5;7.5. Aurora Kinase Inhibitors;45
6.9.6;7.6. Immune System Modulators;45
6.10;8. GENERAL ISSUES ;47
6.10.1;8.1. Which Patients Are Candidates for Targeted Therapies?;47
6.10.2;8.2. New Response Criteria;48
6.10.3;8.3. Clinical Trial Design;48
6.11;REFERENCES;49
7;Targeted Therapy in Breast Cancer;53
7.1;CONTENTS;53
7.2;Abstract;53
7.3;1. INTRODUCTION;53
7.4;2. MOLECULAR MECHANISMS INVOLVED FOR BREAST CANCER GROWTH AND PATIENT SURVIVAL ;55
7.4.1;2.1. Hormone Receptors;55
7.4.2;2.2. Receptor Tyrosine Kinases;55
7.4.3;2.3. Key Signaling Pathways for Breast Cancer;57
7.5;3. TARGETED THERAPIES FOR THE TREATMENT OF BREAST CANCER;58
7.5.1;3.1. Modulation of Estrogen Receptor Signaling;58
7.5.2;3.2. Targeting the HER Signaling Pathway;59
7.5.3;3.3. Targeting VEGF for the Treatment of Breast Cancer;63
7.5.4;3.4. Other Targeted Drugs for Breast Cancer Therapy;64
7.6;4. FUTURE DIRECTION OF TARGETED THERAPY FOR BREAST CANCER;64
7.7;REFERENCES;65
8;Targeted Therapy in Chronic Lymphocytic Leukemia;70
8.1;CONTENTS;70
8.2;Abstract;70
8.3;1. INTRODUCTION;71
8.3.1;1.1. Current Therapies;71
8.3.2;1.2. Prognosis;76
8.4;2. MOLECULAR MECHANISMS PERTINENT TO DISEASE;77
8.5;3. TARGETED THERAPIES ;77
8.5.1;3.1. Alemtuzumab;77
8.5.2;3.2. Rituximab;78
8.5.3;3.3. Alemtuzumab and Rituximab;83
8.5.4;3.4. Ofatumumab;83
8.5.5;3.5. Lenalidomide;83
8.5.6;3.6. Vaccines and Gene Therapy;87
8.5.7;3.7. Lumiliximab;87
8.5.8;3.8. Flavopiridol;88
8.5.9;3.9. Talabostat;88
8.5.10;3.10. Oblimersen;88
8.5.11;3.11. Gossypol;89
8.5.12;3.12. Obatoclax;89
8.5.13;3.13. Heat Shock Protein 90 Inhibitors;89
8.5.14;3.14. Targeted Therapies in Advanced Experimental Trials;89
8.6;4. FUTURE DIRECTIONS IN MOLECULAR THERAPEUTICS;90
8.7;REFERENCES;91
9;Targeted Therapy in Chronic Myeloid Leukemia;96
9.1;CONTENTS;96
9.2;Abstract;96
9.3;1. INTRODUCTION;97
9.4;2. IMATINIB: FRONTLINE THERAPY FOR CML;98
9.4.1;2.1. Survival Advantage;98
9.4.2;2.2. Long-Term Safety;99
9.4.3;2.3. Imatinib Dose Schedules;99
9.4.4;2.4. Monitoring Response to Imatinib Therapy and Minimal Residual Disease;100
9.4.5;2.5. Imatinib Resistance;100
9.4.6;2.6. Overcoming Imatinib Resistance;101
9.5;3. DASATINIB;101
9.5.1;3.1. Optimizing Dose and Schedule;102
9.5.2;3.2. Frontline Therapy;102
9.6;4. NILOTINIB;103
9.6.1;4.1. Frontline Therapy;103
9.7;5. BOSUTINIB (SKI606);104
9.8;6. INNO-406;104
9.9;7. OTHER AGENTS;104
9.10;8. IMMUNOTHERAPY AND RESIDUAL DISEASE;104
9.11;9. CONCLUSION AND FUTURE PERSPECTIVES;105
9.12;REFERENCES;105
10;Targeted Therapy in Colorectal Cancer;109
10.1;CONTENTS;109
10.2;Abstract;109
10.3;1. INTRODUCTION;109
10.3.1;1.1. Overview of Treatment;110
10.3.2;1.2. Familial Predispositions;111
10.4;2. MOLECULAR MECHANISMS;112
10.4.1;2.1. Tumorigenesis Pathways;112
10.4.2;2.2. Cytokine Mechanisms;115
10.5;3. MOLECULAR TARGETED THERAPIES;116
10.5.1;3.1. VEGF;117
10.5.2;3.2. EGFR;119
10.5.3;3.3. Combination of VEGF and EGFR;121
10.5.4;3.4. Other Agents in Late Development;122
10.6;4. FUTURE DIRECTIONS OF MOLECULAR THERAPEUTICS;123
10.6.1;4.1. Moving Beyond EGFR and VEGF;123
10.6.2;4.2. Efficient Trial Design;124
10.6.3;4.3. Translating Our Understanding of Colorectal Biology to the Clinical Setting;124
10.6.4;4.4. Conclusions;125
10.7;5. REFERENCES;125
11;Targeted Therapy in Non-Small Cell Lung Cancer;132
11.1;CONTENTS;132
11.2;Summary;132
11.3;1. INTRODUCTION;132
11.4;2. PUTATIVE TARGETS AND AGENTS IN NSCLC: ErbB FAMILY MEMBERS;133
11.4.1;2.1. Epidermal Growth Factor Receptor;133
11.4.2;2.2. Anti-erbB2 Antibodies;147
11.5;3. PUTATIVE TARGETS AND AGENTS IN NSCLC: VASCULAR ENDOTHELIAL GROWTH FACTOR AND ITS RECEPTOR;147
11.5.1;3.1. Bevacizumab;147
11.5.2;3.2. VEGF Trap (AVE0005);148
11.5.3;3.3. ZD6474 (Vandetanib);148
11.5.4;3.4. Sorafenib (BAY 43-9006);149
11.5.5;3.5. Sunitinib;149
11.5.6;3.6. Axitanib (AG-013736);149
11.5.7;3.7. Nitroglycerin;149
11.6;4. NSCLC AND OTHER ANTIANGIOGENIC AGENTS;149
11.6.1;4.1. CXCL8 (Interleukin-8) and CXCR2 Antagonists;149
11.6.2;4.2. Matrix Metalloproteinase Inhibitors;150
11.6.3;4.3. Interferons;150
11.7;5. OTHER INHIBITORS TO GROWTH IN NSCLCs ;151
11.7.1;5.1. Src Inhibitors;151
11.7.2;5.2. KRAS Inhibitors;151
11.7.3;5.3. Insulin-like Growth Factor and Its Receptor and the Receptor Inhibitors;151
11.7.4;5.4. mTOR Inhibitors;152
11.7.5;5.5. Protein Kinase C Inhibitors;152
11.7.6;5.6. Proteosome Inhibitors;153
11.7.7;5.7. Retinoid X Receptor Targeting;153
11.7.8;5.8. Cyclooxygenase-2 Inhibitors;153
11.7.9;5.9. SGN-15;154
11.8;6. CONCLUSION;154
11.9;REFERENCES;154
12;Targeted Therapy in Lymphoma;164
12.1;CONTENTS;164
12.2;Abstract;164
12.3;1. INTRODUCTION;164
12.4;2. TARGETING SURFACE ANTIGENS ;165
12.4.1;2.1. CD20;165
12.4.2;2.2. CD22;166
12.4.3;2.3. CD19;167
12.4.4;2.4. CD40;168
12.4.5;2.5. CD30;168
12.4.6;2.6. CD80;169
12.4.7;2.7. CD2;170
12.4.8;2.8. CD52;170
12.4.9;2.9. Interleukin-13;170
12.5;3. TARGETING SURFACE RECEPTORS ;170
12.5.1;3.1. Anti-TRAIL Death Receptors;170
12.5.2;3.2. BAFF and its Receptors;171
12.5.3;3.3. RANK Ligand (RANKL) and its Receptors;172
12.6;4. TARGETING LYMPHOMA CELLS WITH SMALL MOLECULES ;172
12.6.1;4.1. Proteasome Inhibitors;172
12.6.2;4.2. mTOR Inhibitors;173
12.6.3;4.3. Heat Shock Protein Inhibitors;175
12.6.4;4.4. Histone Deacetylases Inhibitors;176
12.6.5;4.5. Bcl-2;178
12.6.6;4.6. BCL6;179
12.6.7;4.7. Mitotic Kinases;179
12.6.8;4.8. Protein Kinase (CPKC)-;181
12.6.9;4.9. Extracellular Signal-Regulated Kinase;181
12.7;5. TARGETING TUMOR ANGIOGENESIS;181
12.7.1;5.1. Targeting VEGF and its Receptors;181
12.8;REFERENCES;182
13;Targeted Therapy in Melanoma;190
13.1;CONTENTS;190
13.2;Summary;190
13.3;1. INTRODUCTION;191
13.4;2. SIGNALING PATHWAYS ;192
13.4.1;2.1. RAS/RAF/MAPK Pathway;192
13.4.2;2.2. PI3K/AKT/mTOR Pathway;195
13.4.3;2.3. NF B;197
13.5;3. RECEPTOR TYROSINE KINASE INHIBITORS;198
13.6;4. PROAPOTOTIC PATHWAYS ;199
13.6.1;4.1. Bcl-2;199
13.7;5. POLY(ADP-RIBOSE) POLYMERASE INHIBITORS;201
13.8;6. ANTIANGIOGENESIS STRATEGIES;201
13.8.1;6.1. VEGF Targeting;202
13.8.2;6.2. Thalidomide and Immunomodulatory Drugs;202
13.8.3;6.3. Anti-integrins;204
13.9;7. ANTI-CTLA-4 ANTIBODY;205
13.10;8. FUTURE DIRECTIONS;209
13.11;REFERENCES;210
14;Targeted Therapy in Multiple Myeloma;219
14.1;CONTENTS;219
14.2;Abstract;219
14.3;1. INTRODUCTION;220
14.4;2. MOLECULAR PATHOGENESIS OF MULTIPLE MYELOMA;220
14.5;3. ROLE OF THE MYELOMA CELL AND ITS MICROENVIRONMENT;223
14.5.1;3.1. Multiple Myeloma Cells and Adhesion Molecules;223
14.5.2;3.2. Cytokines;224
14.5.3;3.3. Signaling Cascades in the Development of Multiple Myeloma;225
14.6;4. THERAPIES TARGETING MM CELLS IN THE BONE MARROW MICROENVIRONMENT;226
14.6.1;4.1. Thalidomide and its IMiD Analogues;226
14.6.2;4.2. Thalidomide Maintenance Therapy;228
14.6.3;4.3. Other Lenalidomide-Based Combination Regimens;228
14.6.4;4.4. Proteasome Inhibitors and NF;229
14.6.5;4.4. Proteasome Inhibitors and NF B as a Therapeutic Target: Bortezomib (PS-341, Velcade);229
14.6.6;4.5. Arsenic Trioxide;232
14.7;5. OTHER TARGETED AGENTS IN EARLY DVELOPMENT;233
14.7.1;5.1. RAS as a Therapeutic Target and Farnesylation Inhibitors;233
14.7.2;5.2. Bcl-2 as a Therapeutic Target;234
14.7.3;5.3. Heat Shock Protein-90 as a Therapeutic Target: KOS-953;235
14.7.4;5.4. Histone Deacetylase as a Therapeutic Target: SAHA;235
14.8;6. CONCLUSION AND FUTURE;236
14.9;REFERENCES;236
15;Targeted Therapy in Myelodysplastic Syndrome;243
15.1;CONTENTS;243
15.2;Abstract;243
15.3;1. BACKGROUND;244
15.4;2. MOLECULAR PATHOGENESIS OF MDS;246
15.5;3. TARGETED AGENTS FOR THE TREATMENT OF MDS ;247
15.5.1;3.1. Epigenetic Therapy;247
15.5.2;3.2. Antiangiogenesis Inhibitors;254
15.5.3;3.3. Signal Transduction Inhibitors;258
15.5.4;3.4. Targeting EVI1 Overexpression;260
15.5.5;3.5. Vaccination Approaches for MDS;260
15.6;4. FUTURE DIRECTION OF MOLECULAR THERAPEUTICS IN MDS;261
15.7;REFERENCES;262
16;Targeted Therapy in Epithelial Ovarian Cancer;267
16.1;CONTENTS;267
16.2;Abstract;267
16.3;1. EPIDEMIOLOGY AND NATURAL HISTORY OF OVARIAN CANCER;267
16.4;2. MANAGEMENT OF ADVANCED OVARIAN CANCER;268
16.5;3. UNIQUE ASPECTS OF OVARIAN CANCER PERMITTING STUDY OF NOVEL MANAGEMENT STRATEGIES;269
16.6;4. POTENTIAL FOR “TARGETED THERAPY” OF OVARIAN CANCER;270
16.7;5. EXPERIENCE WITH “TARGETED THERAPY” OF OVARIAN CANCER ;271
16.7.1;5.1. HER2 Overexpression;271
16.7.2;5.2. Epidermal Growth Factor Receptor Overexpression;271
16.7.3;5.3. Tyrosine Kinase Inhibition;271
16.7.4;5.4. Antiangiogenesis Agents;272
16.8;6. CONCLUSION;273
16.9;REFERENCES;273
17;Targeted Drug Therapy in Pancreatic Cancer;276
17.1;CONTENTS;276
17.2;Abstract;276
17.3;1. INTRODUCTION;277
17.4;2. BIOLOGY OF THE DISEASE;278
17.5;3. AGENTS TARGETING EPIDERMAL GROWTH FACTOR RECEPTOR;279
17.6;4. AGENTS TARGETING THE KRAS PROTO- ONCOGENE;282
17.7;5. AGENTS TARGETING VASCULAR ENDOTHELIAL GROWTH FACTOR;282
17.8;6. AGENTS TARGETING MATRIX METALLOPROTEINASES;283
17.9;7. AGENTS INHIBITING PHOSPHOINOSITOL-3-KINASE;284
17.10;8. AGENTS TARGETING SIGNAL TRANSDUCER AND ACTIVATOR OF TRANSCRIPTION 3;285
17.11;9. AGENTS TARGETING TRANSCRIPTION FACTOR NUCLEAR FACTOR- B;286
17.12;10. AGENTS TARGETING BCL-2/ADENOVIRUS E1B 19-KDA PROTEIN- INTERACTING PROTEIN;287
17.13;11. PATIENT SELECTION AND TRIAL DESIGN FOR STUDIES WITH TARGETED AGENTS ;287
17.13.1;11.1. Patient Population Heterogeneity;287
17.13.2;11.2. Appropriate Endpoints to Assess Drug Activity;288
17.13.3;11.3. Changes in Trial Design;288
17.14;12. CONCLUSION;288
17.15;REFERENCES;289
18;Targeted Therapy in Prostate Cancer;293
18.1;CONTENTS;293
18.2;Abstract;293
18.3;1. INTRODUCTION;293
18.4;2. TARGETING THE ANDROGEN RECEPTOR;294
18.4.1;2.1. Reducing Circulating Androgen Concentrations;294
18.4.2;2.2. Modulating Protein Levels and Activation of the AR;296
18.4.3;2.3. Targeting Nongenomic Mechanisms of AR Activation by Signaling Cross- Talk;296
18.5;3. TARGETING ANTIAPOPTOTIC PROTEINS;298
18.6;4. TARGETING PATHWAYS RELATED TO ANGIOGENESIS;299
18.7;5. TARGETING PATHWAYS IN BONE METASTASIS;300
18.8;6. HARNESSING IMMUNOTHERAPEUTIC AGENTS;301
18.8.1;6.1. Modifying T-Cell Co-stimulatory Pathways;301
18.8.2;6.2. Boosting Host Antigen Presentation;302
18.9;7. CONCLUSION;303
18.10;REFERENCES;303
19;Targeted Therapy in Renal Cell Carcinoma;309
19.1;CONTENTS;309
19.2;Abstract;309
19.3;1. EPIDEMIOLOGY;309
19.4;2. PATHOLOGY AND GENETICS;310
19.5;3. MOLECULAR BIOLOGY;310
19.6;4. TARGETING AGENTS FOR RENAL CELL CARCINOMA;312
19.6.1;4.1. Bevacizumab (Avastin);312
19.6.2;4.2. Sorafenib (Bay 43-9006);313
19.6.3;4.3. Sunitinib (Sutent);313
19.6.4;4.4. Axitinib (AG-013736);314
19.6.5;4.5. Temsirolimus (CCI-779);314
19.6.6;4.6. Epidermal Growth Factor Blocking Agents;314
19.7;5. SUMMARY AND FUTURE DIRECTIONS;316
19.7.1;5.1. Pharmacokinetics and Pharmacodynamics;316
19.7.2;5.2. Necessity Versus Sufficiency of Pathway Inhibition;316
19.7.3;5.3. Inherent or Acquired Resistance to Therapy;317
19.8;REFERENCES;317
20;Targeted Therapy of Sarcoma;321
20.1;CONTENTS;321
20.2;Abstract;321
20.3;1. INTRODUCTION ;321
20.3.1;1.1. Overview of Soft Tissue Sarcomas and Bone Tumors;321
20.3.2;1.2. Molecular Alterations in Soft Tissue Sarcomas and Bone Tumors;322
20.4;2. TARGETED THERAPIES;325
20.4.1;2.1. Targeting Growth Factor Pathways;325
20.4.2;2.2. KIT Receptor Tyrosine Kinase in Gastrointestinal Stromal Tumors;326
20.4.3;2.3. Platelet-Derived Growth Factor in Dermatofibrosarcoma Protuberans;328
20.4.4;2.4. ALK Kinase in Inflammatory Myofibroblastic Tumors;330
20.4.5;2.5. Desmoid Tumor–ER Inhibition;331
20.4.6;2.6. Inducing Apoptosis;332
20.4.7;2.7. Apo2 Ligand/TRAIL and Bone Tumors;332
20.4.8;2.8. Rhabdomyosarcoma and Potential Therapeutic Targets;334
20.5;3. CONCLUSIONS;335
20.6;REFERENCES;335
21;Targeted and Functional Imaging;339
21.1;CONTENTS;339
21.2;Abstract;339
21.3;1. INTRODUCTION;340
21.4;2. CLINICAL USE OF FUNCTIONAL IMAGING;340
21.5;3. IMAGING IN CLINICAL TRIALS;341
21.6;4. IMAGING AGENTS;342
21.7;5. MEASURING TARGET DIRECTLY VERSUS DOWNSTREAM EFFECTS;342
21.8;6. NUCLEAR MEDICINE IMAGING ;346
21.8.1;6.1. Radiopharmaceuticals;346
21.8.2;6.2. Physics;346
21.8.3;6.3. PET Physics Introduction;346
21.9;7. MAGNETIC RESONANCE ;352
21.9.1;7.1. Physics;352
21.10;8. DCE-MRI;355
21.10.1;8.1. DCE-MR Physics;356
21.10.2;8.2. Clinical Trials Using DCE-MRI;357
21.11;9. MR SPECTROSCOPY ;359
21.11.1;9.1. Physics;359
21.11.2;9.2. Clinical Trials Using MR Spectroscopy;360
21.12;10. BIOPSY;362
21.13;11. FUTURE OF TARGETED IMAGING;362
21.14;REFERENCES;363
22;Combining Targeted Therapies;365
22.1;CONTENTS;365
22.2;Abstract;365
22.3;1. INTRODUCTION;366
22.4;2. WHY COMBINE ANTICANCER AGENTS AND SPECIFICALLY TARGETED THERAPIES?;366
22.5;3. TARGETED AGENTS IN COMBINATION WITH CYTOTOXIC CHEMOTHERAPEUTIC AGENTS;367
22.5.1;3.1. Experience With Trastuzumab;367
22.5.2;3.2. Lessons from the Use of EGFR Tyrosine Kinase Inhibitors as Targeted Agents;368
22.5.3;3.3. Importance of Timing When Combining Targeted Therapy and Cytotoxic Chemotherapy;369
22.6;4. COMBINATIONS OF MOLECULARLY TARGETED ANTICANCER AGENTS;370
22.6.1;4.1. Underlying Mechanisms of Tumorigenesis and Combination Therapies: Pertinent Considerations;370
22.6.2;4.2. Lessons Learned from Sorafenib and its Combinations;372
22.6.3;4.3. Signaling Pathways and Cross Talk in Combination Therapies;372
22.6.4;4.4. Variables to Consider When Designing Effective Combinations of Targeted Agents;377
22.6.5;4.5. Multitargeted Agents and Combination Treatment Design;377
22.7;5. IMPROVING PRECLINICAL MODELS;378
22.8;6. MOVING TOWARD PERSONALIZED COMBINATIONS;378
22.9;7. BARRIERS TO COMBINATORIAL TARGETED THERAPY IN CANCER TREATMENT;381
22.10;REFERENCES;383
23;Drug Development in Cancer Medicine: Challenges for Targeted Approaches;386
23.1;CONTENTS;386
23.2;Abstract;386
23.3;1. INTRODUCTION;387
23.4;2. SELECTION OF TARGETS FOR CANCER THERAPEUTICS;388
23.4.1;2.1. Signal Transduction Pathways;388
23.4.2;2.2. Cellular Differentiation;388
23.4.3;2.3. Cellular Migration/Invasion;393
23.4.4;2.4. Cellular Survival/Programmed Cell Death;395
23.4.5;2.5. Angiogenesis;395
23.4.6;2.6. Immune Modulation;396
23.5;3. CHALLENGES ASSOCIATED WITH TARGETED ANTICANCER AGENTS ;396
23.5.1;3.1. Drug-Related Challenges;396
23.5.2;3.2. Target-Related Challenges;398
23.5.3;3.3. Tumor-Related Challenges;400
23.6;4. DRUG DEVELOPMENT PROCESS;401
23.6.1;4.1. Clinical Development and Marketing Approval;401
23.6.2;4.2. Study Endpoints;402
23.7;5. CONSIDERATIONS OF POTENTIAL FUTURE APPROACHES;403
23.7.1;5.1. Imatinib Mesylate: Outlier or Precursor of a New Era of Successful Therapies in Cancer Medicine?;403
23.7.2;5.2. Targeted Therapies Against Solid Malignancies: As Successful as Those Directed Against Their Hematologic Counterparts?;405
23.7.3;5.3. Combined Therapies;405
23.7.4;5.4. Tumor Tissue Banking;406
23.7.5;5.5. Prompt Access to Investigational Compounds;407
23.8;6. CONCLUSIONS;407
23.9;REFERENCES;408
24;Toward Personalized Therapy for Cancer;414
24.1;CONTENTS;414
24.2;Abstract;414
24.3;1. INTRODUCTION;414
24.4;2. WHY IS PERSONALIZED MEDICINE IMPORTANT IN CANCER?;415
24.5;3. TO WHAT EXTENT IS CANCER MEDICINE ALREADY PERSONALIZED?;415
24.6;4. FUTURE OF PERSONALIZED MEDICINE IN CANCER;419
24.7;5. CHALLENGES FOR ACHIEVING PERSONALIZED MEDICINE;422
24.8;6. CONCLUSION;425
24.9;REFERENCES;425
25;Index;429