Reportlinker Adds Drug Delivery in Cancer - technologies, markets and companies
NEW YORK, Oct. 5 /PRNewswire/ --Reportlinker.com announces that a new market research report is available in its catalogue:
Drug Delivery in Cancer - technologies, markets and companies
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 2009-2019 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 209 companies involved in developing innovative cancer therapies and methods of delivery are presented along with their 232 collaborations. The bibliography contains over 600 publications that are cited in the report. The report is supplemented with 57 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
Cancer biomarkers . 32
Molecular imaging of cancer 32
Cancer genomics 32
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 49
TAPET (Tumor Amplified Protein Expression Therapy) 50
Bacterial protein for targeted delivery of liposomal cancer drugs . 50 - 4 -
Killed but metabolically active (KBMA) bacteria 50
Bacterial toxins targeted to tumors 51
Immunotoxins 51
Escherichia Coli toxins . 51
Engineered anthrax toxin . 52
Recombinant fusion toxins . 52
Type III secretion systems 53
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 . 55
Cancer drug/gene delivery by mesenchymal stem cells . 56
Cancer immunotherapy 56
Cytokines 56
Cancer vaccines . 57
5T4 as a target for cancer immunotherapy . 58
Anti-telomerase vaccine . 58
Antigen-specific cancer vaccines . 58
Carcinoembryonic antigen-based vaccines 59
Dendritic cells for cancer vaccination . 60
Hybrid cell vaccination . 61
Adoptive cell therapy . 62
Tumor cell vaccines . 64
Vaccines that simultaneously target different cancer antigens . 65
Concluding remarks about cancer vaccines 65
Chemoimmunotherapy . 65
Cancer Vaccine Consortium . 66
Innovative methods of radiation delivery 66
Image-guided ultrasound technology for delivery of radiation 66
Respiratory gating technology for radiation therapy . 66
Positron therapy 67
Boron neutron capture therapy 67
Application of drug delivery systems to BNCP . 67
Use of nanotechnology to enhance BNCT . 68
Skeletal Targeted Radiotherapy . 68
Irreversible electroporation . 69
Methods to overcome multidrug resistance (MDR) 69
P-glycoprotein-mediated MDR . 70
MDR-associated protein gene 70
Strategies for overcoming MDR 70
Blocking the action of P-glycoprotein . 70
Combination of targeted drugs with different specificities . 71
Enzyme Catalyzed Therapeutic Activation 71
Inhibition of DNA repair . 71
Iron chelators that overcomes resistance to chemotherapeutics 72
Liposome formulation of drugs 72
Modification of the chemical structure of the anticancer drug 72
Managing resistance to antiapoptotic action of anticancer agents 73
Modulation of SPARC expression . 73
Nitric oxide inducers 73
Proton pump inhibitors 73
Repression of Prohibitin1 in drug-resistant cancer cells 74
Targeted cancer therapies . 74
Targeting cellular pathways . 74
Targeting antigens in virus-associated cancer 75
Targeting HAAH for cancer therapy 75
Targeting mitochondrial membranes 75
Targeting tumor lymphatics. 77
Targeting tyrosine kinase receptors 77
Inhibitors of bcr-abl tyrosine kinase 77
Inhibition of multiple tyrosine kinases 78
Inhibitors of ErbB tyrosine kinase 78
Targeting the Hedgehog signaling pathway . 79
Targeting caspase-8 . 79
Targeting oncogenes 80
Targeting miRNA for cancer therapeutics 80
Targeting the transferrin receptor-mediated endocytosis pathway 81
Targeted anticancer therapies based on the Rad51 promoter . 81
Targeting cancer stem cells . 81
Targeting glycolytic pathway in cancer 82
Targeting glycoproteins 82 - 5 -
Tagging cancer with modified sugars . 83
Anticancer agents based on glycobiology . 83
Targeting cell surface glycoproteins . 83
Biofusion for targeted cancer therapy 84
Enhancing the effects of radiation and chemotherapy . 84
Sensitizing agents for chemotherapy 84
Tesmilifene for chemosensitization 85
CoFactor to enhance the efficacy of chemotherapy 85
Enzyme-enhanced chemotherapy 85
Sensitizing agents for radiotherapy 86
IPdR 86
Manipulation of tumor oxygenation 86
Hypoxia-based methods to enhance chemotherapy and radiotherapy 86
Hyperbaric oxygen and radiation . 87
HIF-1 antagonists to enhance radiotherapy 87
Nonsteroidal antiinflammatory drugs enhance tumor radiosensitivity . 88
ONCONASE as radiosensitivity enhancer 88
Hyperthermia and chemotherapy/radiation therapy 88
Techniques for hyperthermia 88
Trimodality therapy: radiation, chemotherapy, and hyperthermia . 89
Photodynamic therapy 89
Novel anticancer agents 91
Anti-EphA2 antibodies 92
Antioxidants 92
Brostallicin 92
Agents disrupting folate metabolism . 93
Pemetrexed 93
Cell cycle inhibitors 93
Cytotoxic ribonucleases 93
DNA hypomethylating agents 94
Histone-based cancer therapy . 94
Histone deacetylase inhibitors 94
Modulation of p300/CBP histone acetyltransferase activity . 95
Simulation of endogenous histone for anticancer therapy . 95
HSP90 inhibitors 96
Ion channel blockers 96
IOT-101 . 96
Endovion . 96
LPAAT-beta inhibitors . 97
Modulation of pyruvate kinase M2 97
P13-kinase inhibitors 97
PARP inhibitors 98
Targeted destruction of BRCA2 deficient tumors by PARP inhibitors . 98
Prodrugs . 99
Enzyme-activated prodrugs 99
Ascorbic acid as a prodrug for cancer 99
Prolarix 99
Protein kinase G activation 100
Proteasome inhibitors . 100
Recombinant human insulin-like growth factor binding protein-3 100
Second generation nucleosides 101
Targeting topoisomerase IB 101
Telomerase inhibitors . 102
Therapeutic strategies based on the P53 pathway 102
Therapeutic strategies based on molecular mechanisms 103
In vivo models for molecularly anticancer drugs 103
Checkpoint activation as a strategy against cancer 103
Deletion-specific targeting for cancer therapy . 104
Repair-blocking drugs for enhancing effect of chemotherapy 104
Combining novel anticancer approaches 105
Personalized therapy of cancer 106
Challenges of cancer classification 108
Design of future cancer therapies . 108
Personalized drug development in oncology 109
Role of molecular imaging 109
Role of molecular imaging in targeted cancer therapy 110
Screening for personalized anticancer drugs . 110
Targeting pathways for personalized cancer therapy 111
3. Drug delivery systems for cancer . 113
Introduction 113 - 6 -
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
Polyamine conjugates as anticancer agents . 127
Bacterial ghosts as drug delivery systems for anticancer drugs 127
Microparticles as therapeutic delivery systems in cancer . 127
Subcutaneous injection of microspheres carrying anticancer drugs 128
Intravascular delivery systems using microparticles 128
Tumor embolization with drug-eluting beads 129
Tumor embolization with radioactive microparticles . 129
Microparticles heated by magnetic field 129
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 131
Anticancer drugs bound to protein microspheres . 132
Nanoerythrosomes 132
Micronized droplets of olive oil 132
Nanobiotechnology-based drug delivery for cancer . 132
Nanoparticle formulations for drug delivery in cancer . 134
Anticancer drug particles incorporated in liposomes . 134
Encapsulating drugs in hydrogel nanoparticles 135
Exosomes 136
Folate-linked nanoparticles . 136
Lipid based nanocarriers 137
Micelles for drug delivery in cancer 137
Minicells for targeted delivery of nanoscale anticancer therapeutics . 138
Nanodiamonds for local delivery of chemotherapy at site of cancer . 139
Nanoparticle formulation for enhancing anticancer efficacy of cisplatin . 139
Nanoparticle formulations of paclitaxel. 139
Nanoparticles containing albumin and antisense oligonucleotides 140
Non-aggregating nanoparticles . 140
Pegylated nanoliposomal formulation . 140
Perfluorocarbon nanoparticles . 141
Polypeptide-doxorubicin conjugated nanoparticles . 141
Protosphere nanoparticle technology . 141
Nanoparticles for targeted delivery of drugs into the cancer cells . 142
Antiangiogenic therapy using nanoparticles 143
Carbon magnetic nanoparticles for targeted drug delivery in cancer 144 - 7 -
Carbon nanotubes for targeted drug delivery to cancer cells . 144
DNA aptamer-micelle for targeted drug delivery in cancer 144
Fullerenes for enhancing tumor targeting by antibodies . 145
Gold nanoparticles for targeted drug delivery in cancer 145
Iron oxide magnetic nanoparticle formulation for drug delivery . 146
Lipoprotein nanoparticles targeted to cancer-associated receptors 146
Magnetic nanoparticles for remote-controlled drug delivery to tumors . 147
Nanobees for targeted delivery of cytolytic peptide melittin 147
Nanocell for targeted drug delivery to tumor 148
Nanodroplets for site-specific cancer treatment. 148
Nanoparticle-mediated targeted delivery of peptides into tumors 149
Nanoparticle-mediated targeting of MAPK signaling pathway 149
Nanoparticles for targeted delivery of concurrent chemoradiation 149
Nanostructured hyaluronic acid for targeted drug delivery in cancer 150
Phage nanoparticles as antibody-drug conjugates . 150
Polymer nanoparticles for targeted drug delivery in cancer . 150
Polymersomes for targeted cancer drug delivery . 151
Targeted drug delivery with nanoparticle-aptamer bioconjugates 151
Dendrimers for anticancer drug delivery . 152
Application of dendrimers in boron neutron capture therapy . 153
Application of dendrimers in photodynamic therapy . 153
Dendrimer-based synthetic vector for targeted cancer gene therapy . 154
Devices for nanotechnology-based cancer therapy . 154
Convection-enhanced delivery with nanoliposomal CPT-11 . 154
Nanocomposite devices 154
Nanoengineered silicon for brachytherapy 155
Nanosensors for targeted drug delivery in cancer 155
Nanoparticles combined with physical agents for tumor ablation 155
Carbon nanotubes for laser-induced cancer destruction . 155
Nanoparticles and thermal ablation . 156
Nanoparticles combined with ultrasound radiation of tumors 157
Nanoparticles as adjuncts to photodynamic therapy of cancer. 157
Nanoparticles for boron neutron capture therapy 158
RNA nanotechnology for delivery of cancer therapeutics . 158
Nanocarriers for simultaneous delivery of multiple anticancer agents 158
Combination of diagnostics and therapeutics for cancer 159
Biomimetic nanoparticles targeted to tumors 159
Dendrimer nanoparticles for targeting and imaging tumors 159
Gold nanoparticle plus bombesin for imaging and therapy of cancer 159
Gold nanorods for diagnosis plus photothermal therapy of cancer . 159
Magnetic nanoparticles for imaging as well as therapy of cancer . 160
Nanobialys for combining MRI with delivery of anticancer agents 160
pHLIP nanotechnology for detection and targeted therapy of cancer 161
Radiolabeled carbon nanotubes for tumor imaging and targeting 161
Targeted therapy with magnetic nanomaterials guided by antibodies . 161
Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles 161
Polyethylene glycol technology 162
Enzon's PEG technology . 162
Debiopharm's PEG biconjugate drug delivery platform . 163
Nektar PEGylation . 163
PEG Intron . 163
Single-chain antibody-binding protein technology 164
Vesicular systems for drug delivery in cancer 164
Liposomes for anticancer drug delivery . 164
Antibody-targeted liposomes for cancer therapy . 165
AlZA's Stealth liposomes 165
Boron-containing liposomes 166
DepoFoam technology . 166
Hyperthermia and liposomal drug delivery . 166
Liposomal doxorubicin formulation with N-octanoyl-glucosylceramide 167
Liposome-nucleic acid complexes for anticancer drug delivery 167
Non-pegilated liposomal doxorubicin . 168
Tumor-selective targeted drug delivery via folate-PEG liposomes 168
Ultrasound-mediated anticancer drug release from liposomes . 168
Companies developing liposome-based anticancer drugs 168
Pharmacosomes for controlled anticancer drug delivery 169
Emulsion formulations of anticancer drugs 170
Albumin-based drug carriers . 170
Anticancer drugs that bind to tumors 171
Monoclonal antibodies . 171
Murine monoclonal antibodies 171 - 8 -
Humanized MAbs . 171
Actions and uses of monoclonal antibodies in cancer 172
Targeted antibody-based cancer therapy 173
Antibody–cytokine fusion proteins . 173
Antibody J591 for targeted delivery of anticancer therapy 173
Anti-Thomsen-Friedenreich antigen MAb 173
Combining MAbs with anti-CD55 antibody 173
MAbs targeted to alpha fetaprotein receptor . 174
MAbs targeted to tumor blood vessels . 174
MAbs targeted to HAAH . 174
MAbs for immune activation 175
Delivery of cancer therapy with MAbs . 175
Antibody-directed enzyme prodrug therapy . 176
Chemically programmed antibodies 176
Combining diagnostics with therapeutics based on MAbs . 177
Radiolabeled antibodies 177
Clinical development of MAbs for treatment of cancer . 178
Advantages and limitations of MAbs for cancer therapy . 183
Monoclonal T cell receptors . 184
Radioactive materials for diagnosis and targeted therapy of cancer 184
Pretargeted radioimmunotherapy of cancer . 184
Radiolabeled somatostatin receptor antagonists . 185
Theophylline enhances radioiodide uptake by cancer 185
Strategies for drug delivery in cancer 185
Direct introduction of anticancer drugs into the tumor 186
Injection into the tumor . 186
Antineoplastic drug implants into tumors . 187
Tumor necrosis therapy . 187
Injection into the arterial blood supply of cancer . 188
Electrochemotherapy . 189
Pressure-induced filtration of drugs across vessels to the tumor . 190
Improving drug transport to tumors . 190
Carbohydrate-enhanced chemotherapy 190
Dextrans as macromolecular anticancer drug carriers 191
In situ production of anticancer agents in tumors 191
Targeted drug delivery in cancer 191
Affibody molecules for targeted anticancer therapy . 192
Fatty acids as targeting vectors 193
Genetic targeting of the kinase activity in cancer cells . 193
Heat-activated targeted drug delivery 194
Novel transporters to target photosensitizers to cancer cell nuclei . 194
Photodynamic therapy of cancer . 194
Radionuclides delivered with receptor targeting technology 195
Targeting ligands specific for cancer cells . 195
Targeting abnormal DNA in cancer cells . 196
Targeting using a bispecific antibody . 196
Targeted chemotherapy using transporters 196
Targeted generation of intracellular reactive oxygen species. 197
Targeted delivery to receptors found in tumors . 197
Targeted delivery by tumor-activated prodrug therapy 197
Targeting glutathione S-transferase 199
Targeting tumors by exploiting leaky blood vessels . 199
Targeted drug delivery of anticancer agents with controlled activation . 200
Targeted delivery of anticancer agents with ReCODE™ technology 200
Transmembrane Carrier Systems 201
Transferrin-oligomers as targeting carriers in anticancer drug delivery. 201
Tumor targeting with peptides 201
Ultrasound and microbubbles for targeted anticancer drug delivery . 201
Ultrasound for targeted delivery of chemotherapeutics 202
Vitamin B12 and folate for targeting cancer chemotherapy . 203
Drug delivery in relation to circadian rhythms 204
Implants for systemic delivery of anticancer drugs . 205
Drug-eluting polymer implants . 205
Angiogenesis and drug delivery to tumors . 205
Antiangiogenesis strategies . 206
Targeting tumor endothelial cells 206
Methods for overcoming limitations of antiangiogenesis approaches 207
Vascular targeting agents . 207
Alpha-emitting antibodies for vascular targeting . 208
Angiolytic therapy . 208
Anti-phosphatidylserine antibodies as VTA . 208 - 9 -
ASA404 . 209
Cadherin inhibitors 209
Combretastatin A4 Prodrug 210
Drugs to induce clotting in tumor vessels . 210
Selective permeation of the anticancer agent into the tumor 211
Targeted delivery of tissue factor 211
Vascular targeting agents versus antiangiogenesis agents 212
ZD6126 . 212
Delivery of proteins and peptides for cancer therapy 213
CELLECTRA™ electroporation device 214
Emisphere's eligen™ system 214
Diatos Peptide Vector intra-cellular/intra-nuclear delivery technology 214
Lytic peptides and cancer . 215
Modification of proteins and peptides with polymers 215
Peptide-based targeting of cancer biomarkers for drug delivery 215
Peptide-cytokine complexes as vascular targeting agents . 216
Peptide-polymer conjugates with radionuclides . 216
Transduction of proteins in vivo 217
Tumor targeting by stable toxin (ST) peptides 217
A computational approach to integration of drug delivery methods for cancer 217
4. Delivery of Biological Therapies for Cancer . 219
Introduction 219
Antisense therapy 219
Basics of antisense approaches 219
Antisense cancer therapy 219
Mechanisms of anticancer effect of antisense oligonucleotides . 220
Selected antisense drugs in development for cancer . 220
Antisense targeted to ribonucleotide reductase . 220
Immune modulatory oligonucleotide 221
Ribozyme therapy 221
Antisense drug delivery issues . 222
Strategies to overcome delivery problems of antisense oligonucleotides 222
Antisense delivery in microspheres 222
Delivery of antisense using nanoparticles . 223
Delivery across the blood-brain barrier 223
Delivery of ribozymes 224
Iontophoretic delivery of oligonucleotides . 224
Liposomes-mediated oligonucleotide delivery . 224
Neugene? antisense drugs 224
Oral delivery of oligonucleotides . 225
Peptide nucleic acid delivery . 225
Receptor-mediated endocytosis 225
Delivery of ribozymes 226
Combination of antisense and electrochemotherapy . 226
Aptamers for combined diagnosis and therapeutics of cancer 227
Antisense compounds in clinical trials . 227
RNA interference . 228
Basics of RNAi . 228
Comparison of antisense and RNAi . 228
RNAi applications in oncology 229
siRNA-based cancer immunotherapy 230
Delivery of siRNA in cancer . 230
Delivery of siRNA by nanoparticles 231
Delivery of siRNA by nanosize liposomes 231
Lipid nanoparticles for delivery of anticancer siRNAs 232
Polymer nanoparticles for targeted delivery of anticancer siRNA 232
Companies developing cancer therapies based on antisense and RNAi 233
DNA interference . 234
Cancer gene therapy 234
Basics of gene therapy . 234
Strategies for cancer gene therapy . 235
Gene transfer techniques as applied to cancer gene therapy 236
Viral vectors . 236
Non-viral vectors 237
A polymer approach to gene therapy for cancer 237
Direct gene delivery to the tumor 238
Injection into tumor 238
Reversible electroporation 239
Hematopoietic gene transfer . 240
Genetic modification of human hematopoietic stem cells 240 - 10 -
Gene-based strategies for immunotherapy of cancer (immunogene therapy) . 241
Cytokine gene therapy . 241
Monoclonal antibody gene transfer . 245
Transfer and expression of intracellular adhesion-1 molecules . 245
Other gene-based techniques of immunotherapy of cancer 245
Fas (Apo-1) 245
Chemokines . 245
Major Histocompatibility Complex (MHC) Class I . 246
IGF (Insulin-Like Growth Factor) . 246
Inhibition of immunosuppressive function . 246
Delivery of toxic genes to tumor cells for eradication (molecular chemotherapy) 247
Gene-directed enzyme prodrug therapy . 247
Combination of gene therapy with radiotherapy . 248
Multipronged therapy of cancer with microencapsulated cells 248
Correction of genetic defects in cancer cells (mutation compensation) 249
Targeted gene therapy for cancer 249
Transcriptional targeting for cancer gene therapy 249
Targeted epidermal growth factor-mediated DNA delivery 250
Gene-based targeted drug delivery to tumors . 250
Targeting gene expression to hypoxic tumor cells . 251
Targeting gene expression by progression-elevated gene-3 promoter 251
Targeted delivery of retroviral particles hitchhiking on T cells . 251
Targeting tumors with genetically modified T cells . 252
Targeting tumors by genetically engineered stem cells 252
Tumor-targeted gene therapy by receptor-mediated endocytosis 253
Targeted site-specific delivery of anticancer genes by nanoparticles 253
Immunolipoplex for delivery of p53 gene . 253
Combination of electrogene and electrochemotherapy . 254
Virus-mediated oncolysis 254
Targeted cancer treatments based on oncolytic viruses 254
Oncolytic gene therapy 254
Cytokine-induced killer cells for delivery of an oncolytic virus . 255
Facilitating oncolysis by targeting innate antiviral response by HDIs 255
Oncolytic HSV . 256
Oncolytic adenoviruses 256
Oncolytic Coxsackie virus A21 258
Oncolytic vesicular stomatitis virus 258
Oncolytic measles virus . 258
Oncolytic paramyxovirus 259
Oncolytic reovirus . 259
Oncolytic vaccinia virus 259
Cancer terminator virus . 260
Monitoring of viral-mediated oncolysis by PET. 260
Companies developing oncolytic viruses . 261
Antiangiogenic therapy for cancer 261
Apoptotic approach to improve cancer gene therapy. 262
Bacteria as novel anticancer gene vectors . 262
Concluding remarks on cancer gene therapy . 263
Cancer gene therapy companies 264
Cell therapy for cancer . 266
Cellular immunotherapy for cancer . 267
Treatments for cancer by ex vivo mobilization of immune cells 267
Granulocytes as anticancer agents . 268
Neutrophil granulocytes in antibody-based immunotherapy of cancer . 268
Use of hematopoietic stem cells for targeted cancer therapy . 268
Cancer vaccines . 269
Cell-based cancer vaccines 269
Autologous tumor cell vaccines . 269
Vaccines that simultaneously target different cancer antigens . 270
Delivery systems for cell-based cancer vaccines 270
Nucleic acid-based cancer vaccines 271
DNA cancer vaccines . 271
Antiangiogenic DNA cancer vaccine . 271
Methods of delivery of DNA vaccines . 272
RNA vaccines 273
Viral vector-based cancer vaccines . 273
Companies involved in nucleic acid-based vaccines 273
Genetically modified cancer cells vaccines . 274
GVAX cancer vaccines . 275
Genetically modified dendritic cells 275
Multipeptide-based cancer vaccines 276 - 11 -
5. Delivery strategies according to cancer type and location 277
Introduction 277
Bladder cancer . 277
Intravesical drug delivery 277
Intravesical agents combined with systemic chemotherapy . 277
Targeted anticancer therapy for bladder cancer . 278
Prodrug EOquin for bladder cancer . 278
Antisense treatment of bladder cancer 279
Gene therapy for bladder cancer 279
Brain tumors 280
Methods for evaluation of anticancer drug penetration into brain tumor 280
Innovative methods of drug delivery for glioblastoma multiforme . 280
Anticancer agents with increased penetration of BBB 281
Nanoparticle delivery across the BBB for imaging and therapy of brain tumors 282
Intranasal perillyl alcohol 282
Combination of chemotherapy with radiotherapy . 283
Local delivery of chemotherapeutic agents into the tumor . 283
Carmustine biodegradable polymer implants 283
Fibrin glue implants containing anticancer drugs. 284
Biodegradable microspheres containing 5-FU 284
Magnetically controlled microspheres . 284
Convection-enhanced delivery . 284
Receptor-directed cytotoxin therapy 284
Delivery of a modified diphtheria toxin conjugated to transferrin . 285
Convection-enhanced delivery with nanoliposomal CPT-11 . 285
Monoclonal antibodies targeted to brain tumors . 286
Liposomes for drug delivery to brain tumors 286
Use of nanoparticles for drug delivery in glioblastoma multiforme 287
Lipid-coated microbubbles as a delivery vehicle for taxol. 287
Targeted antiangiogenic/apoptotic/cytotoxic therapies for brain tumors 288
Multiple targeted drugs for brain tumors . 288
Introduction of the chemotherapeutic agent into the CSF pathways 289
Intraventricular chemotherapy for meningeal cancer . 289
Intrathecal chemotherapy 290
Increasing the permeability of blood-tumor barrier to anticancer drugs. 290
BBB disruption 290
Nanoparticle-based targeted delivery of chemotherapy across the BBB 291
Tyrosine kinase inhibitor increases topotecan penetration into CNS . 291
Intraarterial chemotherapy . 292
Interstitial delivery of dexamethasone for reduction of peritumor edema 293
Photodynamic therapy for chemosensitization of brain tumors . 293
Nanoparticles for photodynamic therapy of brain tumors 293
Innovative delivery of radiotherapy to brain tumors . 294
GliaSite Radiation Therapy System 294
Boron neutron capture therapy for brain tumors . 294
Cell therapy for glioblastoma multiforme . 294
Mesenchymal stem cells to deliver treatment for gliomas . 294
Gene therapy for glioblastoma multiforme. . 295
Single-chain antibody-targeted adenoviral vectors 296
Intravenous gene delivery with nanoparticles into brain tumors 296
Neural stem cells for drug/gene delivery to brain tumors . 297
Peptides targeted to glial tumor cells . 298
Targeting normal brain cells with an AAV vector encoding interferon-?. 298
Treatment of medulloblastoma by suppressing genes in Shh pathway . 298
Antiangiogenic gene therapy 299
Anticancer drug delivery by genetically engineered MSCs . 299
RNAi gene therapy of brain cancer 299
Ligand-directed delivery of dsRNA molecules targeted to EGFR . 300
Virus-mediated oncolytic therapy of brain cancer 300
Vaccination for glioblastoma multiforme 302
Breast Cancer 302
Therapies for breast cancer involving innovative methods of drug delivery 303
Injectable biodegradable polymer delivery system for local chemotherapy 303
MammoSite brachytherapy 304
Monoclonal antibodies for breast cancer 304
Breast cancer vaccines . 305
HER-2 DNA AutoVac? vaccine 305
Recombinant adenoviral ErbB-2/neu vaccine 306
Gene vaccine for breast cancer . 306
NeuVax 307
Gene therapy for breast cancer 307 - 12 -
Antisense therapy for breast cancer . 307
Inhibitors of growth factors FGF2 and VEGF for breast cancer 308
Targeted multi-drug delivery approach to breast cancer 308
Cancer of the cervix and the uterus . 308
Gene therapy for cervical cancer 309
Delivery of chemoradiation therapy 309
Cervical cancer vaccines . 309
Colorectal cancer . 309
Perifosine 310
Cancer of the liver . 310
Hepatocellular carcinoma 310
Treatment of liver metastases . 311
Leukemia . 312
Clofarabine 312
Malignant melanoma . 312
Targeted therapies for melanoma 313
Immunotherapy for malignant melanoma . 313
Gene therapy for malignant melanoma . 314
Neuroblastoma 316
Genetically modified NSCs for treatment of neuroblastoma . 316
Non-Hodgkin's lymphoma 316
Pixantrone 317
Non-small cell lung cancer . 317
Aerosol delivery of anticancer agents for lung cancer 318
Aerosol gene delivery for lung cancer . 319
Complex nanoscale pulmonary delivery of drugs for resistant lung cancer . 319
Intratumoral administration of anticancer drugs through a bronchoscope 319
Ovarian cancer . 319
Innovative drug delivery for ovarian cancer . 320
Intraperitoneal delivery 320
Gene Therapy for ovarian cancer . 321
Pancreatic cancer 321
Targeted chemotherapy for pancreatic cancer . 322
Local anticancer drug delivery
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