Drug Delivery in Cancer - Technologies, Markets and Companies
NEW YORK, Nov. 30, 2011 /PRNewswire/ -- Reportlinker.com announces that a new market research report is available in its catalogue:
Drug Delivery in Cancer - technologies, markets and companies
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Summary
Drug delivery remains a challenge in management of cancer. Approximately 12.5 million new cases of cancer are being diagnosed worldwide each year and considerable research is in progress for drug discovery for cancer. Cancer drug delivery is no longer simply wrapping up cancer drugs in a new formulations for different routes of delivery. The focus is on targeted cancer therapy. The newer approaches to cancer treatment not only supplement the conventional chemotherapy and radiotherapy but also prevent damage to normal tissues and prevent drug resistance.
Innovative cancer therapies are based on current concepts of molecular biology of cancer. These include antiangiogenic agents, immunotherapy, bacterial agents, viral oncolysis, targeting of cyclic-dependent kinases and tyrosine kinase receptors, antisense approaches, gene therapy and combination of various methods. Important methods of immunotherapy in cancer involve use of cytokines, monoclonal antibodies, cancer vaccines and immunogene therapy.
Several innovative methods of drug delivery are used in cancer. These include use of microparticles as carriers of anticancer agents. These may be injected into the arterial circulation and guided to the tumor by magnetic field for targeted drug delivery. Polyethylene glycol (PEG) technology has been used to overcome some of the barriers to anticancer drug delivery. Encapsulating anticancer drugs in liposomes enables targeted drug delivery to tumor tissues and prevents damage to the normal surrounding tissues. Monoclonal antibodies can be used for the delivery of anticancer payloads such as radionucleotides, toxins and chemotherapeutic agents to the tumors.
Antisense oligonucleotides have been in clinical trials for cancer for some time now. RNAi has also been applied in oncology. Small interfering RNAs (siRNAs) can be targeted to tumors and one example is suppression of H-ras gene expression indicating the potential for application in therapy of ovarian cancer. Cancer gene therapy is a sophisticated form of drug delivery for cancer. Various technologies and companies developing them are described. Nucleic acid-based cancer vaccines are also described.
Drug delivery strategies vary according to the type and location of cancer. Role of drug delivery in the management of cancers of the brain, the bladder, the breast, the ovaries and the prostate are used as examples to illustrate different approaches both experimental and clinical. Biodegradable implants of carmustine are already used in the treatment of malignant brain tumors.
The market value of drug delivery technologies and the anticancer drugs are difficult to separate. Cancer market estimates from 2010-2020 are given according to organs involved and the types of cancer as well as according to technologies. Distribution of the into major regions is also described.
Profiles of 212 companies involved in developing innovative cancer therapies and methods of delivery are presented along with their 241 collaborations. The bibliography contains over 600 publications that are cited in the report.The report is supplemented with 58 tables and 8 figures.
TABLE OF CONTENTS
0. Executive Summary 17
1. Introduction to cancer therapy 19
Molecular biology of cancer 19
The genesis of cancer 19
Normal cell cycle and growth 19
Oncogenes 20
Tumor Suppressor Genes 20
Role of microRNAs in cancer 22
Role of Bub 1 gene in cell division 22
Mechanism of DNA damage in Fanconi anemia leading to leukemia 23
Accumulation of random mutations 23
Chromosomal instability 23
Aneuploidy 24
Telomeres and cancer 24
DNA methylation and cancer 25
Anticancer treatments based on RNA regulation of genes 25
Hallmarks of cancer 26
Self-sufficiency of tumor proliferation 26
Apoptosis 27
Therapeutic implications of apoptosis in cancer 27
Autophagy 29
Tumor angiogenesis 29
Acquisition of a potential for unlimited replication 31
Invasion and metastases 31
Tumor suppressor genes and metastases 32
Cancer biomarkers 32
Molecular imaging of cancer 32
Cancer genomics 33
Gene expression profiling in cancer 33
Cancer proteomics 33
Limitations of genomics and proteomics for understanding cancer 34
Cancer microenvironment 34
Epidemiology of cancer 35
Current management of cancer 35
Chemotherapy 36
Limitations of cancer chemotherapy 36
Radiotherapy 36
Brachytherapy 37
Surgery 37
Basics of drug delivery in cancer 37
Historical landmarks in cancer drug delivery 37
2. Innovative treatments for cancer 39
Introduction 39
Selective estrogen receptor modulators 40
Antiangiogenic strategies for cancer 41
Development of antiangiogenic therapies 41
Classification of antiangiogenic agents 41
Examples of antiangiogenic agents 43
Chemotherapy at lower than maximum tolerated dose 43
Galectin-3 as a target for inhibiting angiogenesis 43
Inhibitors of endothelial proliferation 43
Inducers of apoptosis of endothelial cells of tumor vessels 44
Lodamin 44
Matrix metalloproteinase inhibitors 44
Monoclonal antibodies with vasculostatic properties 45
PPAR? agonists 46
Rapalogues as antiangiogenic agents 47
VEGF Trap 47
Agents that decrease the permeability of tumor blood vessels 47
Antiangiogenic agents in clinical trials 48
Combination of antiangiogenic with cytotoxic therapy 48
Bacterial anticancer agents 48
Tumor-targeted bacteria 49
Genetically modified Salmonella typhimurium as anticancer agent 50
TAPET (Tumor Amplified Protein Expression Therapy) 50
Bacterial protein for targeted delivery of liposomal cancer drugs 50
Killed but metabolically active (KBMA) bacteria 51
Bacterial toxins targeted to tumors 51
Immunotoxins 51
Escherichia Coli toxins 51
Engineered anthrax toxin 52
Recombinant fusion toxins 52
Type III secretion systems 54
Induction of apoptosis in cancer by bacterial proteins 54
Induction of immune response by bacteriolytic therapy 54
Innovations in cell therapy for cancer 55
Stem cell transplantation for cancer 56
Cancer drug/gene delivery by mesenchymal stem cells 56
Cancer immunotherapy 56
Cytokines 57
Cancer vaccines 57
5T4 as a target for cancer immunotherapy 58
Anti-telomerase vaccine 59
Antigen-specific cancer vaccines 59
Carcinoembryonic antigen-based vaccines 60
Dendritic cells for cancer vaccination 60
Hybrid cell vaccination 62
Adoptive cell therapy 63
Tumor cell vaccines 64
Vaccines that simultaneously target different cancer antigens 65
Concluding remarks about cancer vaccines 66
Chemoimmunotherapy 66
Cancer Vaccine Consortium 66
Innovative methods of radiation delivery 66
Image-guided ultrasound technology for delivery of radiation 67
Respiratory gating technology for radiation therapy 67
Positron therapy 67
Boron neutron capture therapy 68
Application of drug delivery systems to BNCP 68
Use of nanotechnology to enhance BNCT 68
Skeletal Targeted Radiotherapy 69
Irreversible electroporation 69
Methods to overcome multidrug resistance (MDR) 70
P-glycoprotein-mediated MDR 70
MDR-associated protein gene 70
Strategies for overcoming MDR 71
Blocking the action of P-glycoprotein 71
Combination of targeted drugs with different specificities 71
Enzyme Catalyzed Therapeutic Activation 72
Inhibition of DNA repair 72
Iron chelators that overcomes resistance to chemotherapeutics 72
Liposome formulation of drugs 73
Modification of the chemical structure of the anticancer drug 73
Managing resistance to antiapoptotic action of anticancer agents 73
Modulation of SPARC expression 74
Nitric oxide inducers 74
Proton pump inhibitors 74
Repression of Prohibitin1 in drug-resistant cancer cells 74
Targeted cancer therapies 75
Targeting cellular pathways 75
Targeting antigens in virus-associated cancer 75
Targeting HAAH for cancer therapy 76
Targeting the IGF-I receptor 76
Targeting Mcl-1 protein 76
Targeting mitochondrial membranes 76
Targeting tumor lymphatics 78
Targeting tyrosine kinase receptors 78
Inhibitors of bcr-abl tyrosine kinase 79
Inhibition of multiple tyrosine kinases 79
Inhibitors of ErbB tyrosine kinase 79
Targeting the Hedgehog signaling pathway 80
Targeting caspase-8 80
Targeting oncogenes 81
Targeting miRNA for cancer therapeutics 82
Targeting the transferrin receptor-mediated endocytosis pathway 82
Targeted anticancer therapies based on the Rad51 promoter 82
Targeting cancer stem cells 82
Targeting glycolytic pathway in cancer 83
Targeting glycoproteins 84
Tagging cancer with modified sugars 84
Anticancer agents based on glycobiology 84
Targeting cell surface glycoproteins 84
Biofusion for targeted cancer therapy 85
Enhancing the effects of radiation and chemotherapy 85
Sensitizing agents for chemotherapy 86
Tesmilifene for chemosensitization 86
CoFactor to enhance the efficacy of chemotherapy 86
Enzyme-enhanced chemotherapy 86
Sensitizing agents for radiotherapy 87
IPdR 87
Manipulation of tumor oxygenation 87
Hypoxia-based methods to enhance chemotherapy and radiotherapy 88
Hyperbaric oxygen and radiation 88
HIF-1 antagonists to enhance radiotherapy 89
Nonsteroidal antiinflammatory drugs enhance tumor radiosensitivity 89
ONCONASE as radiosensitivity enhancer 89
Hyperthermia and chemotherapy/radiation therapy 89
Techniques for hyperthermia 90
Trimodality therapy: radiation, chemotherapy, and hyperthermia 90
Photodynamic therapy 91
Novel anticancer agents 93
Anti-EphA2 antibodies 93
Antioxidants 93
Brostallicin 93
Agents disrupting folate metabolism 94
Pemetrexed 94
Cell cycle inhibitors 94
Cytotoxic ribonucleases 95
DNA hypomethylating agents 95
Histone-based cancer therapy 95
Histone deacetylase inhibitors 95
Modulation of p300/CBP histone acetyltransferase activity 96
Simulation of endogenous histone for anticancer therapy 96
HSP90 inhibitors 97
Ion channel blockers 97
IOT-101 97
Endovion 98
LPAAT-beta inhibitors 98
Modulation of pyruvate kinase M2 98
P13-kinase inhibitors 98
PARP inhibitors 99
Targeted destruction of BRCA2 deficient tumors by PARP inhibitors 99
Prodrugs 100
Enzyme-activated prodrugs 100
Ascorbic acid as a prodrug for cancer 100
Prolarix 101
Protein kinase G activation 101
Proteasome inhibitors 101
Recombinant human insulin-like growth factor binding protein-3 102
Second generation nucleosides 102
Targeting topoisomerase IB 103
Telomerase inhibitors 103
Therapeutic strategies based on the P53 pathway 104
Therapeutic strategies based on molecular mechanisms 104
Checkpoint activation as a strategy against cancer 104
Deletion-specific targeting for cancer therapy 105
In vivo models for molecularly anticancer drugs 105
Repair-blocking drugs for enhancing effect of chemotherapy 106
Targeting mTOR signaling defects 106
Combining novel anticancer approaches 106
Personalized therapy of cancer 107
Challenges of cancer classification 109
Design of future cancer therapies 110
Personalized drug development in oncology 110
Role of molecular imaging 110
Role of molecular imaging in targeted cancer therapy 111
Screening for personalized anticancer drugs 112
Targeting pathways for personalized cancer therapy 112
3. Drug delivery systems for cancer 113
Introduction 113
Routes of drug delivery in cancer 113
Intravenous delivery systems for cancer therapy 114
Intravenous versus oral ascorbate for treatment of cancer 115
Subcutaneous injection of anticancer agents 115
Oral delivery of anticancer agents 115
Oral UFT 116
5-FU combined with eniluracil 116
Oral paclitaxel 117
Oral fluoropyrimidines 117
Oral satraplatin 118
Oral PXD101 118
ARRY-142886 119
High dose pulse administration of calcitrol 119
Oral gefitinib vs intravenous docetaxel 119
Transdermal drug delivery 119
Delivery of the photosensitizer drug ?-amino levulinic acid 120
Transdermal delivery of the methotrexate 120
Transdermal nitroglycerine for prostate cancer 120
Transdermal delivery of peptide cancer vaccines 121
Intradermal delivery of cancer vaccines by adenoviral vectors 121
Pulmonary delivery of anticancer agents 121
Regional intra-arterial delivery of chemotherapy 122
Gas embolotherapy of tumors 122
Drug delivery to lymph nodes 123
Intraperitoneal macrophages as drug delivery vehicle 123
Challenges of cancer drug delivery 123
Tumor blood vessel pore barrier to drug delivery 123
Improvement of drug transport in tumors 124
Delivery of anticancer drugs to nuclear targets 124
Innovative formulations for drug delivery in cancer 125
Cancer targeting with polymeric drugs 125
Linking anticancer drugs to polyglutamate 126
Improving delivery of protein-polymer anticancer drugs 126
Macromolecules as delivery systems for taxanes 127
Polyamine conjugates as anticancer agents 127
Bacterial ghosts as drug delivery systems for anticancer drugs 127
Microparticles as therapeutic delivery systems in cancer 128
Subcutaneous injection of microspheres carrying anticancer drugs 128
Intravascular delivery systems using microparticles 129
Tumor embolization with drug-eluting beads 129
Tumor embolization with radioactive microparticles 129
Microparticles heated by magnetic field 130
Magnetic targeted microparticle technology 130
Release of drugs from micelles by ultrasound 130
Release of drugs from biSphere by ultrasound 131
Release of drugs from microcapsules by laser 131
Chemoembolization 131
Anticancer drugs bound to carbon particles 132
Anticancer drugs bound to protein microspheres 132
Nanoerythrosomes 132
Micronized droplets of olive oil 132
Nanobiotechnology-based drug delivery for cancer 133
Nanoparticle formulations for drug delivery in cancer 134
Anticancer drug particles incorporated in liposomes 134
Encapsulating drugs in hydrogel nanoparticles 136
Exosomes 136
Folate-linked nanoparticles 137
Lipid based nanocarriers 137
Micelles for drug delivery in cancer 137
Minicells for targeted delivery of nanoscale anticancer therapeutics 139
Nanobombs for cancer 139
Nanodiamonds for local delivery of chemotherapy at site of cancer 140
Nanoparticle formulation for enhancing anticancer efficacy of cisplatin 140
Nanoparticle formulations of paclitaxel 140
Nanoparticles containing albumin and antisense oligonucleotides 141
Non-aggregating nanoparticles 141
Pegylated nanoliposomal formulation 141
Perfluorocarbon nanoparticles 142
Polypeptide-doxorubicin conjugated nanoparticles 142
Protosphere nanoparticle technology 142
Nanoparticles for targeted delivery of drugs into the cancer cells 143
Antiangiogenic therapy using nanoparticles 144
Carbon magnetic nanoparticles for targeted drug delivery in cancer 144
Carbon nanotubes for targeted drug delivery to cancer cells 145
DNA aptamer-micelle for targeted drug delivery in cancer 145
Fullerenes for enhancing tumor targeting by antibodies 145
Gold nanoparticles for targeted drug delivery in cancer 146
Iron oxide magnetic nanoparticle formulation for drug delivery 147
Lipoprotein nanoparticles targeted to cancer-associated receptors 147
Magnetic nanoparticles for remote-controlled drug delivery to tumors 148
Nanobees for targeted delivery of cytolytic peptide melittin 148
Nanocell for targeted drug delivery to tumor 149
Nanodroplets for site-specific cancer treatment 149
Nanoparticle-mediated targeted delivery of peptides into tumors 150
Nanoparticle-mediated targeting of MAPK signaling pathway 150
Nanoparticles for targeted delivery of concurrent chemoradiation 150
Nanostructured hyaluronic acid for targeted drug delivery in cancer 151
Nanoparticles as antibody-drug conjugates 151
Nanoparticle-coated peptides for tumor targeting 151
Polymer nanoparticles for targeted drug delivery in cancer 151
Polymersomes for targeted cancer drug delivery 152
Targeted drug delivery with nanoparticle-aptamer bioconjugates 152
Dendrimers for anticancer drug delivery 153
Application of dendrimers in boron neutron capture therapy 154
Application of dendrimers in photodynamic therapy 154
Dendrimer-based synthetic vector for targeted cancer gene therapy 155
Devices for nanotechnology-based cancer therapy 155
Convection-enhanced delivery with nanoliposomal CPT-11 155
Nanocomposite devices 155
Nanoengineered silicon for brachytherapy 156
Nanosensors for targeted drug delivery in cancer 156
Nanoparticles combined with physical agents for tumor ablation 156
Carbon nanotubes for laser-induced cancer destruction 157
Nanoparticles and thermal ablation 157
Nanoparticles combined with ultrasound radiation of tumors 158
Nanoparticles as adjuncts to photodynamic therapy of cancer 158
Nanoparticles for boron neutron capture therapy 159
RNA nanotechnology for delivery of cancer therapeutics 159
Nanocarriers for simultaneous delivery of multiple anticancer agents 160
Multistage nanoparticle delivery system for penetration into tumor tissue 160
Combination of diagnostics and therapeutics for cancer 160
Biomimetic nanoparticles targeted to tumors 160
Dendrimer nanoparticles for targeting and imaging tumors 160
Gold nanoparticle plus bombesin for imaging and therapy of cancer 161
Gold nanorods for diagnosis plus photothermal therapy of cancer 161
Magnetic nanoparticles for imaging as well as therapy of cancer 162
Nanobialys for combining MRI with delivery of anticancer agents 162
pHLIP nanotechnology for detection and targeted therapy of cancer 162
Radiolabeled carbon nanotubes for tumor imaging and targeting 163
Targeted therapy with magnetic nanomaterials guided by antibodies 163
Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles 163
Future prospects of nanobiotechnology and targeted cancer therapy 164
Polyethylene glycol technology 164
Enzon's PEG technology 164
Debiopharm's PEG biconjugate drug delivery platform 165
Nektar PEGylation 165
PEG Intron 165
Single-chain antibody-binding protein technology 166
Vesicular systems for drug delivery in cancer 166
Liposomes for anticancer drug delivery 167
Antibody-targeted liposomes for cancer therapy 167
AlZA's Stealth liposomes 168
Boron-containing liposomes 168
DepoFoam technology 168
Hyperthermia and liposomal drug delivery 169
Liposomal doxorubicin formulation with N-octanoyl-glucosylceramide 169
Liposome-nucleic acid complexes for anticancer drug delivery 169
Non-pegilated liposomal doxorubicin 170
Tumor-selective targeted drug delivery via folate-PEG liposomes 170
Ultrasound-mediated anticancer drug release from liposomes 170
Companies developing liposome-based anticancer drugs 170
Pharmacosomes for controlled anticancer drug delivery 171
Emulsion formulations of anticancer drugs 172
Albumin-based drug carriers 173
Anticancer drugs that bind to tumors 173
Monoclonal antibodies 173
Murine monoclonal antibodies 173
Humanized MAbs 174
Actions and uses of monoclonal antibodies in cancer 174
Targeted antibody-based cancer therapy 175
Antibody–cytokine fusion proteins 175
Antibody J591 for targeted delivery of anticancer therapy 175
Anti-Thomsen-Friedenreich antigen MAb 175
Combining MAbs with anti-CD55 antibody 176
MAbs targeted to alpha fetaprotein receptor 176
MAbs targeted to tumor blood vessels 176
MAbs targeted to HAAH 176
MAbs for immune activation 177
Delivery of cancer therapy with MAbs 177
Antibody-directed enzyme prodrug therapy 178
Chemically programmed antibodies 178
Combining diagnostics with therapeutics based on MAbs 179
Radiolabeled antibodies 179
Clinical development of MAbs for treatment of cancer 181
Advantages and limitations of MAbs for cancer therapy 184
Antibody drug conjugates 186
Monoclonal T cell receptors 187
Radioactive materials for diagnosis and targeted therapy of cancer 187
Pretargeted radioimmunotherapy of cancer 187
Radiolabeled somatostatin receptor antagonists 187
Theophylline enhances radioiodide uptake by cancer 188
Strategies for drug delivery in cancer 188
Direct introduction of anticancer drugs into the tumor 189
Injection into the tumor 189
Antineoplastic drug implants into tumors 190
Tumor necrosis therapy 190
Injection into the arterial blood supply of cancer 191
Electrochemotherapy 192
Pressure-induced filtration of drugs across vessels to the tumor 193
Improving drug transport to tumors 193
Carbohydrate-enhanced chemotherapy 193
Dextrans as macromolecular anticancer drug carriers 193
In situ production of anticancer agents in tumors 194
Targeted drug delivery in cancer 194
Affibody molecules for targeted anticancer therapy 195
Fatty acids as targeting vectors 195
Genetic targeting of the kinase activity in cancer cells 196
Heat-activated targeted drug delivery 196
Novel transporters to target photosensitizers to cancer cell nuclei 197
Photodynamic therapy of cancer 197
Radionuclides delivered with receptor targeting technology 198
Targeting ligands specific for cancer cells 198
Targeting abnormal DNA in cancer cells 199
Targeting using a bispecific antibody 199
Targeted chemotherapy using transporters 199
Targeted generation of intracellular reactive oxygen species 200
Targeted delivery to receptors found in tumors 200
Targeted delivery by tumor-activated prodrug therapy 200
Targeting glutathione S-transferase 202
Targeting tumors by exploiting leaky blood vessels 202
Targeted drug delivery of anticancer agents with controlled activation 203
Targeted delivery of anticancer agents with ReCODE™ technology 203
Transmembrane Carrier Systems 203
Transferrin-oligomers as targeting carriers in anticancer drug delivery 204
Tumor targeting with peptides 204
Ultrasound and microbubbles for targeted anticancer drug delivery 204
Ultrasound for targeted delivery of chemotherapeutics 205
Vitamin B12 and folate for targeting cancer chemotherapy 206
Cell-based drug delivery in cancer 207
Red blood cells as vehicles for drug delivery 207
Cells as vehicles for gene delivery 208
Drug delivery in relation to circadian rhythms 208
Implants for systemic delivery of anticancer drugs 208
Drug-eluting polymer implants 209
Angiogenesis and drug delivery to tumors 209
Antiangiogenesis strategies 210
Targeting tumor endothelial cells 210
Methods for overcoming limitations of antiangiogenesis approaches 211
Vascular targeting agents 211
Alpha-emitting antibodies for vascular targeting 212
Angiolytic therapy 212
Anti-phosphatidylserine antibodies as VTA 212
ASA404 213
Cadherin inhibitors 213
Combretastatin A4 Prodrug 214
Drugs to induce clotting in tumor vessels 214
Selective permeation of the anticancer agent into the tumor 215
Targeted delivery of tissue factor 215
Vascular targeting agents versus antiangiogenesis agents 216
ZD6126 216
Delivery of proteins and peptides for cancer therapy 217
CELLECTRA™ electroporation device 218
Emisphere's eligen™ system 218
Diatos Peptide Vector intra-cellular/intra-nuclear delivery technology 218
Lytic peptides and cancer 219
Modification of proteins and peptides with polymers 219
Peptide-based targeting of cancer biomarkers for drug delivery 219
Peptide-cytokine complexes as vascular targeting agents 220
Peptide-polymer conjugates with radionuclides 220
Transduction of proteins in vivo 221
Tumor targeting by stable toxin (ST) peptides 221
Image-guided personalized drug delivery in cancer 221
A computational approach to integration of drug delivery methods for cancer 222
4. Delivery of Biological Therapies for Cancer 223
Introduction 223
Antisense therapy 223
Basics of antisense approaches 223
Antisense cancer therapy 223
Mechanisms of anticancer effect of antisense oligonucleotides 224
Selected antisense drugs in development for cancer 224
Antisense targeted to ribonucleotide reductase 224
Immune modulatory oligonucleotide 225
Ribozyme therapy 225
Antisense drug delivery issues 226
Strategies to overcome delivery problems of antisense oligonucleotides 226
Antisense delivery in microspheres 226
Delivery of antisense using nanoparticles 227
Delivery across the blood-brain barrier 227
Delivery of ribozymes 228
Iontophoretic delivery of oligonucleotides 228
Liposomes-mediated oligonucleotide delivery 228
Neugene? antisense drugs 228
Oral delivery of oligonucleotides 229
Peptide nucleic acid delivery 229
Receptor-mediated endocytosis 229
Delivery of ribozymes 230
Combination of antisense and electrochemotherapy 230
Aptamers for combined diagnosis and therapeutics of cancer 231
Antisense compounds in clinical trials 231
RNA interference 232
Basics of RNAi 232
Comparison of antisense and RNAi 232
RNAi applications in oncology 233
siRNA-based cancer immunotherapy 234
Delivery of siRNA in cancer 234
Delivery of siRNA by nanoparticles 235
Delivery of siRNA by nanosize liposomes 235
Lipid nanoparticles for delivery of anticancer siRNAs 236
Polymer nanoparticles for targeted delivery of anticancer siRNA 236
Companies developing cancer therapies based on antisense and RNAi 237
DNA interference 238
Cancer gene therapy 238
Basics of gene therapy 238
Strategies for cancer gene therapy 239
Gene transfer techniques as applied to cancer gene therapy 240
Viral vectors 240
Nonviral vectors 241
A polymer approach to gene therapy for cancer 241
Direct gene delivery to the tumor 242
Injection into tumor 242
Reversible electroporation 243
Hematopoietic gene transfer 244
Genetic modification of human hematopoietic stem cells 244
Gene-based strategies for immunotherapy of cancer (immunogene therapy) 245
Cytokine gene therapy 245
Monoclonal antibody gene transfer 249
Transfer and expression of intracellular adhesion-1 molecules 249
Other gene-based techniques of immunotherapy of cancer 249
Fas (Apo-1) 249
Chemokines 249
Major Histocompatibility Complex (MHC) Class I 250
IGF (Insulin-Like Growth Factor) 250
Inhibition of immunosuppressive function 250
microRNA gene therapy 251
Delivery of toxic genes to tumor cells for eradication (molecular chemotherapy) 251
Gene-directed enzyme prodrug therapy 251
Combination of gene therapy with radiotherapy 252
Multipronged therapy of cancer with microencapsulated cells 253
Correction of genetic defects in cancer cells (mutation compensation) 253
Targeted gene therapy for cancer 254
Transcriptional targeting for cancer gene therapy 254
Targeted epidermal growth factor-mediated DNA delivery 254
Gene-based targeted drug delivery to tumors 254
Targeting gene expression to hypoxic tumor cells 255
Targeting gene expression by progression-elevated gene-3 promoter 255
Targeted delivery of retroviral particles hitchhiking on T cells 256
Targeting tumors with genetically modified T cells 256
Targeting tumors by genetically engineered stem cells 256
Tumor-targeted gene therapy by receptor-mediated endocytosis 257
Targeted site-specific delivery of anticancer genes by nanoparticles 257
Immunolipoplex for delivery of p53 gene 257
Combination of electrogene and electrochemotherapy 258
Virus-mediated oncolysis 258
Targeted cancer treatments based on oncolytic viruses 258
Oncolytic gene therapy 259
Cytokine-induced killer cells for delivery of an oncolytic virus 259
Facilitating oncolysis by targeting innate antiviral response by HDIs 260
Oncolytic HSV 260
Oncolytic adenoviruses 260
Oncolytic Coxsackie virus A21 262
Oncolytic vesicular stomatitis virus 262
Oncolytic measles virus 263
Oncolytic paramyxovirus 263
Oncolytic reovirus 263
Oncolytic vaccinia virus 264
Cancer terminator virus 264
Monitoring of viral-mediated oncolysis by PET 264
Companies developing oncolytic viruses 265
Antiangiogenic therapy for cancer 265
Apoptotic approach to improve cancer gene therapy 266
Bacteria as novel anticancer gene vectors 267
Concluding remarks on cancer gene therapy 267
Cancer gene therapy companies 268
Cell therapy for cancer 270
Cellular immunotherapy for cancer 271
Treatments for cancer by ex vivo mobilization of immune cells 271
Granulocytes as anticancer agents 272
Neutrophil granulocytes in antibody-based immunotherapy of cancer 272
Use of hematopoietic stem cells for targeted cancer therapy 272
Cancer vaccines 273
Cell-based cancer vaccines 273
Autologous tumor cell vaccines 273
Vaccines that simultaneously target different cancer antigens 274
Delivery systems for cell-based cancer vaccines 275
Nucleic acid-based cancer vaccines 275
DNA cancer vaccines 275
Antiangiogenic DNA cancer vaccine 276
Methods of delivery of DNA vaccines 276
RNA vaccines 277
Viral vector-based cancer vaccines 277
Companies involved in nucleic acid-based vaccines 277
Genetically modified cancer cells vaccines 278
GVAX cancer vaccines 279
Genetically modified dendritic cells 279
Multipeptide-based cancer vaccines 280
5. Delivery strategies according to cancer type and location 281
Introduction 281
Bladder cancer 281
Intravesical drug delivery 281
Intravesical agents combined with systemic chemotherapy 281
Targeted anticancer therapy for bladder cancer 282
Prodrug EOquin for bladder cancer 282
Antisense treatment of bladder cancer 283
Gene therapy for bladder cancer 283
Brain tumors 284
Methods for evaluation of anticancer drug penetration into brain tumor 284
Innovative methods of drug delivery for glioblastoma multiforme 284
Delivery of anticancer drugs across the blood-brain barrier 285
Anticancer agents with increased penetration of BBB 285
BBB disruption 286
Nanoparticle-based targeted delivery of chemotherapy across the BBB 287
Tyrosine kinase inhibitor increases topotecan penetration into CNS 288
Bypassing the BBB by alternative methods of drug delivery 288
Intranasal perillyl alcohol 288
Intraarterial chemotherapy 289
Enhancing tumor permeability to chemotherapy 289
Local delivery of chemotherapeutic agents into the tumor 290
Carmustine biodegradable polymer implants 290
Fibrin glue implants containing anticancer drugs. 291
Biodegradable microspheres containing 5-FU 291
Magnetically controlled microspheres 291
Convection-enhanced delivery 291
CED for receptor-directed cytotoxin therapy 291
CED of topotecan 292
CED of a modified diphtheria toxin conjugated to transferrin 292
CED of nanoliposomal CPT-11 293
CED for delivery 131I-chTNT-1/B MAb 293
Anticancer drug formulations for targeted delivery to brain tumors 293
Lipid-coated microbubbles as a delivery vehicle for taxol 293
Liposomes for drug delivery to brain tumors 293
MAbs targeted to brain tumors 294
Multiple targeted drugs for brain tumors 294
Nanoparticles for targeted drug delivery in glioblastoma multiforme 295
Targeted antiangiogenic/apoptotic/cytotoxic therapies 296
Introduction of the chemotherapeutic agent into the CSF pathways 297
Intraventricular chemotherapy for meningeal cancer 297
Intrathecal chemotherapy 297
Interstitial delivery of dexamethasone for reduction of peritumor edema 298
Combination of chemotherapy with radiotherapy 298
Photodynamic therapy for chemosensitization of brain tumors 298
Nanoparticles for photodynamic therapy of brain tumors 299
Innovative delivery of radiotherapy to brain tumors 299
GliaSite Radiation Therapy System 299
Boron neutron capture therapy for brain tumors 299
Cell therapy for glioblastoma multiforme 300
Mesenchymal stem cells to deliver treatment for gliomas 300
Gene therapy for glioblastoma multiforme. 300
Antiangiogenic gene therapy 301
Anticancer drug delivery by genetically engineered MSCs 302
Intravenous gene delivery with nanoparticles into brain tumors 302
Ligand-directed delivery of dsRNA molecules targeted to EGFR 302
Neural stem cells for drug/gene delivery to brain tumors 303
Peptides targeted to glial tumor cells 304
RNAi gene therapy of brain cancer 304
Single-chain antibody-targeted adenoviral vectors 304
Targeting normal brain cells with an AAV vector encoding interferon-? 305
Treatment of medulloblastoma by suppressing genes in Shh pathway 305
Virus-mediated oncolytic therapy of brain cancer 305
Vaccination for glioblastoma multiforme 308
Breast Cancer 308
Therapies for breast cancer involving innovative methods of drug delivery 308
Injectable biodegradable polymer delivery system for local chemotherapy 309
MammoSite brachytherapy 309
Monoclonal antibodies targeted to HER2 receptor 309
Breast cancer vaccines 310
HER-2 DNA AutoVac? vaccine 310
Recombinant adenoviral ErbB-2/neu vaccine 311
Gene vaccine for breast cancer 311
NeuVax 312
Gene therapy for breast cancer 313
Antisense therapy for breast cancer 313
Inhibitors of growth factors FGF2 and VEGF for breast cancer 314
Targeted multi-drug delivery approach to breast cancer 314
Cancer of the cervix and the uterus 314
Gene therapy for cervical cancer 314
Delivery of chemoradiation therapy 314
Cervical cancer vaccines 315
Colorectal cancer 315
Perifosine 315
Oxaliplatin long-circuting liposomes 316
Cancer of the liver 316
Hepatocellular carcinoma 316
Treatment of liver metastases 317
Leukemia 317
Clofarabine 318
Malignant melanoma 318
Targeted therapies for melanoma 319
Immunotherapy for malignant melanoma 319
Gene therapy for malignant melanoma 320
Neuroblastoma 322
Genetically modified NSCs for treatment of neuroblastoma 322
Non-Hodgkin's lymphoma 322
Pixantrone 322
Non-small cell lung cancer 323
Aerosol delivery of anticancer agents for lung cancer 324
Aerosol gene delivery for lung cancer 324
Complex nanoscale pulmonary delivery of drugs for resistant lung cancer 325
Intratumoral administration of anticancer drugs through a bronchoscope 325
Ovarian cancer 325
Innovative drug delivery for ovarian cancer 325
Intraperitoneal delivery 326
Dendritic cell vaccination for ovarian cancer 327
Gene Therapy for ovarian cancer 327
Pancreatic cancer 328
Targeted chemotherapy for pancreatic cancer 328
Local anticancer drug delivery for pancreatic cancer 328
Vaccine for pancreatic cancer 329
Gene therapy for pancreatic cancer 329
Adenovirus-mediated transfer of vasostatin gene 329
Rexin-G? for targeted gene delivery in pancreatic cancer 329
Targeted Expression of BikDD gene 330
Prostate cancer 330
PACLIMER Microspheres 331
PRX302 331
Brachytherapy for cancer of prostate 331
Capridine-beta 332
LHRH for prostate cancer 332
LHRH analogs 332
Histrelin implant 333
Immunomodulatory drugs 333
MAbs for prostate cancer 333
Targeted therapies for prostate cancer 334
Delivery of cisplatin to prostate cancer by nanoparticles 334
Delivery of siRNAs to prostate cancer with aptamer-siRNA chimeras 334
Delivery of siRNA for prostate cancer with metastases 334
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