Chapter
TARGETED THERAPY FOR SOLID TUMORS AND HEMATOLOGIC MALIGNANCIES
TARGETED THERAPY FOR SOLID TUMORS AND HEMATOLOGIC MALIGNANCIES
Chapter I Therapeutic Agents and Approaches in the Age of Personalized Cancer Care
I. Novel Anti-Tumor Agents
Small Molecule Inhibitors
Note About Safety And Patient Protection.
Ii. Alternate Approaches To Targeting Tumor
III. Approaches to Analyzing Tumor
Chapter II Optimizing the Development of Targeted Therapies in the Phase I Clinical Trial Setting
1. Background and Overview
2. Phase I Studies and the Rapid Development of Targeted Cancer Therapeutics: The RET/Met/VEGFR2 Inhibitor XL184 and its Direct Progression from a Phase I Study to a Phase III Registration Trial
3. Phase I Trials and the Development of Anticancer Agents from Bench to Bedside: The Anti-IL-6 Antibody CNTO-328 and Castleman’s Disease
4. Phase I Trials and the Development of Anticancer Agents from Bedside to Bench and Back to Bench: IGFR Inhibition and Ewing’s Sarcoma
5. Strategies for Maximizing Data Accrual from Phase I Clinical Trials of Targeted Agents and Trial Efficiency
5.1. The Use of Phase I Patients as their own Internal Controls
5.2. Strategies to Evaluate Combination Treatment with Targeted Agents in Phase I Studies
6. Future Directions in Phase I Oncology Trials of Targeted Agents
Chapter III Targeted Therapy for Chronic Myeloid Leukemia
The CML Target: BCR-ABL1 Kinase
Imatinib Mesylate: The Paradigm of Targeted Therapy in Cancer
Novel TKIs for the Treatment of CML
Chapter IV Targeted Therapy in the Treatment of Lymphocytic Leukemia
Cyclin-dependent Kinase Inhibitors
BCL-2 Family Member Inhibitors
Protein Kinase C Inhibitors
Small Modular Immune Pharmaceutics
Tyrosine Kinase Inhibitors
Chapter V Targeted Therapy in Acute Myeloid Leukemia and Myelodysplastic Syndromes
Clinical Results with FLT3 Inhibitors
Farnesyl Transferase Inhibitors
Clinical Results with TIPIFARNIB in AML
Clinical Results with Tipifarnib in MDS
Clinical Results with Gemtuzumab Ozogamycin
Clinical Results with Immunomodulatory Drugs
Clinical Results with Hypomethylating Agents
Histone Deacetylase Inhibitors
Clinical Results of Histone Deacetylase Inhibitors
Epigenetic Therapy – Combination Trials
Clinical Results with Combination Epigenetic Therapy
Targeted Therapy in Acute Promyelocytic Leukemia
Clinical Results with ATRA in APL
Clinical Results with Arsenic Trioxide in APL
Chapter VI Targeted Strategies for Multiple Myeloma
Chapter VII Targeted Therapy for Breast Cancer
2. Epidermal Growth Factor
2.1. Epidermal Growth Factor Inhibitors
2.2. Dual EGFR and HER2 Inhibitors
Lapatinib as Single Agent
Lapatinib in Combination with Chemotherapy in First-line Metastatic Breast Cancer
Lapatinib in Combination with Trastuzumab
Lapatinib in Combination with Hormonal Agents
3. Insulin-like Growth Factor
Ongoing Trials with Anti-IGF Inhibitors
4. Vascular Endothelial Growth Factor
Phase I-II Studies Bevacizumab Single Agent and Combination with Chemotherapy
Phase III Studies of Bevacizumab in Previously Treated Metastatic Breast Cancer
Phase III Study of Bevacizumab as First Line Metastatic Breast Cancer
Bevacizumab in Combination with other Targeted Therapies
5. Farnesyl Transferase Inhibitors
6. PI3K/Akt/PTEN Pathway Inhibitors
Deforolimus (AP235373 and MK-8669; Ariad Pharmaceuticals Inc, Cambridge, MA)
Chapter VIII Targeted Therapy in Gastrointestinal Carcinomas
Cell Surface Receptor Inhibitors
Epidermal Growth Factor Receptor (EGFR)/anti-EGFR Agents
Vascular Endothelial Growth Factors (VEGFs) and VEGF Receptors (VEGFRs)/Anti-angiogenic Agents
Insulin-like Growth Factor 1 (IGF-1) and IGF-1 Receptor (IGF-1R) Inhibitors
Fibroblast Growth Factor (FGF) and FGF Receptor (FGFR) Inhibitors
Hedgehog (Hh) Pathway Inhibitors
Matrix Metalloproteinase (MMP) Inhibitors
Cell Cycle–associated Inhibitors
Downstream Cell Signal Inhibitors
Ubiquitin-proteasome Pathway Inhibitors
PI3K/AKT/mTOR Pathway Inhibitors
FAK (Focal Adhesion Kinase)/Src
Development of Targeted Therapy in GI Carcinomas
Gastroesophageal Carcinoma
Biliary Tract and Gallbladder Carcinomas
Summary and Future Direction
Chapter IX Targeted Genitourinary Cancers
Targeted Therapies for Bladder Cancer
Inhibition of Human Epidermal Growth Factor Receptors
Testicular and Germ Cell Tumors
Targeted Therapies for Germ Cell Tumors
Targeted Therapies for Prostate Cancer
Endothelin-A (ETA) Receptor Antagonist
Targeted Therapies for Renal Cell Carcinoma
Chapter X Targeted Therapy in Head and Neck Malignancies
Epidermal Growth Factor Receptor Inhibition
Cetuximab does not Reverse Platinum Resistance
Cetuximab Plus Chemotherapy as Front-line Therapy
Cetuximab, Platinum, and 5-FU
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Monotherapy
Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors and Chemotherapy
Anti-epidermal Growth Factor Receptor Oligonucleotides
Resistance to Epidermal Growth Factor Receptor-Targeted Therapy
Other Small Molecule Inhibitors
Targeted Therapy and Radiation
Cetuximab-Cisplatin-Radiation
Current Biomarkers of Drug and Radiation Sensitivity
Need for Better Prognostic and Predictive Biomarkers
Epidermal Growth Factor Receptor
Chapter XI Therapeutic Approaches for Ovarian Cancer
Cellular and Molecular Pathogenesis of Ovarian Cancer
Cellular Origin of Ovarian Cancers
Pathogenesis of Ovarian Cancer
BRCA1, BRCA2, and Familial Ovarian Cancers
Imprinted Tumor Suppressor Genes
Other Epigenetically Silenced Genes (Table 2)
Activation of Signaling Pathways in Ovarian Cancer Cells
Antiangiogenic Therapy in Ovarian Cancer
Challenges for the Future
Chapter XII Targeted Therapy for Endocrine Neoplasms
Targeted Therapy in Neuroendocrine Tumor
Targeted Therapy in Thyroid Cancers (Medullary and Anaplastic)
Medullary Thyroid Carcinoma (MTC)
Anaplastic Thyroid Cancer (ATC)
Targeted Therapy in Adrenal Cancers (Adrenocortical Carcinoma and Pheochromocytomas / Paragangliomas)
Adrenocortical Carcinoma (ACC)
Pheochromocytoma / Paraganglioma
Chapter XIII Targeted Therapeutic Approaches for Cancers of the Central Nervous System
Classification and Grading
Clinical and Pathological Features
Current Conventional Treatment
Genetic Alterations in Brain Tumors
Targeting Signaling Pathways with Specific Agents
Growth Factors–regulated Pathways
Cell Cycle-regulated Pathways
Specific Targets and Respective Agents
HGF/Scatter Factor (SF) Pathway
Challenge in Target Therapies
New Methods of Clinical Design
Chapter XIV Targeting Tumors and Personalizing Individual Treatments for Radiation Therapy
Targeted Therapy with Radiation Biology
Depth Specific Tumor Targeting and Personalization of Treatment as a Function of Technology
Depth Specific Tumor Targeting and Personalization of Treatment as a Function of Radiation Physics
Tumor Area/Volume/Shape Specific Targeting for Patient and Disease Specific Treatment
Two Dimensional Treatment Planning
CT and 3D Conformal Radiation Treatment Planning
Intensity Modulated Radiation Therapy (IMRT)
Image Guided Radiation Therapy
Targeted and Personalized Radiation Therapy thru Technology/Physics
Chemotherapeutic/Biologic Targeting and Personalized Radiation (Synergy and Sensitization)
Molecular Biology of Personalized Radiation Oncology
Predictive Radiosensitivity Assays
Tumor Proliferative Potential (Tpot)
Clonogenic Cell Survival Assay
Expression Profiling through Microarrays
Example of Predicting Outcome: Glioblastoma, Temozolomide, Radiation and MGMT Silencing
Molecular Targeted Therapy: EGFR and Head NS Neck Cancer
Putting it all Together: Tumor Oxygenation Status
Targeted Therapy for Solid Tumors and Hematologic Malignancies
( Cancer Etiology, Diagnosis and Treatments )
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