Drug Delivery in Cancer - technologies, markets and companies |
|
|
0. Executive Summary ...... 15 1. Introduction to cancer therapy.......... 17 Molecular biology of cancer........ 17 The genesis of cancer .17 Normal cell cycle and growth .17 Oncogenes .....18 Tumor Suppressor Genes ......18 Role of Bub 1 gene in cell division .........19 Accumulation of random mutations .......20 Chromosomal instability........20 Aneuploidy .....21 Telomeres and cancer...........21 DNA methylation and cancer..22 Anticancer treatments based on RNA regulation of genes .............22 Hallmarks of cancer....22 Self-sufficiency of tumor proliferation .........23 Apoptosis ............23 Therapeutic implications of apoptosis in cancer ............24 Autophagy......25 Induction of angiogenesis...........25 Acquisition of a potential for unlimited replication..............27 Invasion and metastases............27 Cancer biomarkers 28 Molecular imaging of cancer .......28 Cancer genomics... 29 Gene expression profiling in cancer ............29 Cancer proteomics 30 Limitations of genomics and proteomics for understanding cancer..... 30 Cancer microenvironment .......... 30 Role of hypoxia and miRNA in cancer microenvironment ....31 Epidemiology of cancer .............. 31 Current management of cancer.. 32 Chemotherapy .....32 Limitations of cancer chemotherapy.......32 Radiotherapy .......33 Brachytherapy 33 Surgery ..............33 Basics of drug delivery in cancer 33 Historical landmarks in cancer drug delivery .. 34 2. Innovative treatments for cancer ...... 35 Introduction......... 35 Selective estrogen receptor modulators.... 36 Antiangiogenic agents. 37 Development of antiangiogenic therapies ....37 Classification of antiangiogenic agents ........37 Blocking Akt signaling pathway by rapamycin ..............38 Inhibitors of endothelial proliferation .....39 Inducers of apoptosis of endothelial cells of tumor vessels ...........39 Chemotherapy at lower than maximum tolerated dose..39 Monoclonal antibodies with vasculostatic properties......40 Matrix metalloproteinase inhibitors ........41 PPAR a agonists .....41VEGF Trap......42 Agents that decrease the permeability of tumor blood vessels ......42 Antiangiogenic agents in clinical trials ....42 Combination of antiangiogenic with cytotoxic therapy ........43 Bacterial anticancer agents........ 43 Tumor-targeted bacteria ............44 Genetically modified Salmonella typhimurium as anticancer agent.44 TAPET (Tumor Amplified Protein Expression Therapy) ...44 Bacterial protein for targeted delivery of liposomal cancer drugs ...45 Killed but metabolically active (KBMA) bacteria ..45 Bacterial toxins targeted to tumors.............45 Immunotoxins 45 Escherichia Coli toxins ..........46 - 4 - Engineered anthrax toxin ......46 Recombinant fusion toxins.....47 Type III secretion systems .........48 Induction of apoptosis in cancer by bacterial proteins ........49 Induction of immune response by bacteriolytic therapy......49 Innovations in cell therapy for cancer....... 49 Stem cell transplantation for cancer ...........50 Cancer drug/gene delivery by mesenchymal stem cells......50 Cancer immunotherapy.............. 50 Cytokines...........51 Cancer vaccines ...51 5T4 as a target for cancer immunotherapy ...52 Anti-telomerase vaccine........53 Antigen-specific cancer vaccines. ..........53 Carcinoembryonic antigen-based vaccines....54 Dendritic cells for cancer vaccination .....54 Hybrid cell vaccination ..........55 Lymphocyte-based cancer therapies ......56 Tumor cell vaccines ..............58 Vaccines that simultaneously target different cancer antigens.......59 Concluding remarks about cancer vaccines ..59 Cancer Vaccine Consortium ........59 Innovative methods of radiation delivery . 59 Image-guided ultrasound technology for delivery of radiation ............60 Respiratory gating technology for radiation therapy...........60 Positron therapy ..60 Boron neutron capture therapy ...61 Skeletal Targeted Radiotherapy ..61 Irreversible electroporation....... 62 Methods to overcome multidrug resistance (MDR) ........ 62 P-glycoprotein-mediated MDR.....63 MDR-associated protein gene......63 Strategies for overcoming MDR...63 Blocking the action of P-glycoprotein .....63 Nitric oxide inducers .............64 Managing resistance to antiapoptotic action of anticancer agents ..64 Inhibition of DNA repair ........64 Liposome formulation of drugs..............65 Modification of the chemical structure of the anticancer drug ........65 Enzyme Catalyzed Therapeutic Activation.....65 Modulation of SPARC expression ...........66 Iron chelators that overcomes resistance to chemotherapeutics ....66 Proton pump inhibitors..........66 Combination of targeted drugs with different specificities .............66 Targeted cancer therapies ......... 67 Targeting cellular pathways........67 Targeting antigens in virus-associated cancer ....68 Targeting HAAH for cancer therapy.............68 Targeting mitochondrial membranes...........68 Targeting tumor lymphatics........69 Targeting tyrosine kinase receptors ............70 Inhibitors of bcr-abl tyrosine kinase.......70 Inhibition of multiple tyrosine kinases ....70 Inhibitors of ErbB tyrosine kinase..........71 Targeting the Hedgehog signaling pathway..71 Targeting ras oncogene..............72 Targeting the transferrin receptor-mediated endocytosis pathway ......72 Targeting cancer stem cells ........72 Targeting glycoproteins..............73 Tagging cancer with sugars ...73 Anticancer agents based on glycobiology74 Targeting cell surface glycoproteins .......74 Biofusion for targeted cancer therapy ....74 Targeted drug delivery of anticancer agents with controlled activation 75 Enhancing the effects of radiation and chemotherapy ... 75 Sensitizing agents for chemotherapy ..........75 Tesmilifene for chemosensitization ........75 CoFactor to enhance the efficacy of chemotherapy .......76 Enzyme-enhanced chemotherapy..........76 Sensitizing agents for radiotherapy ............76 IPdR ..............77 - 5 - Manipulation of tumor oxygenation.............77 Hypoxia-based methods to enhance chemotherapy and radiotherapy ..77 Hyperbaric oxygen and radiation ...........78 HIF-1 antagonists to enhance radiotherapy ..78 Nonsteroidal antiinflammatory drugs enhance tumor radiosensitivity ...78 ONCONASE as radiosensitivity enhancer 79 Hyperthermia and chemotherapy/radiation therapy ...........79 Techniques for hyperthermia .79 Trimodality therapy: radiation, chemotherapy, and hyperthermia..80 Photodynamic therapy 80 Novel anticancer agents............. 82 Anti-EphA2 antibodies.82 Antioxidants ........83 Brostallicin ..........83 Agents disrupting folate metabolism...........83 Pemetrexed....83 Cytotoxic ribonucleases..............84 DNA hypomethylating agents......84 Histone deacetylase inhibitors.....84 HSP90 inhibitors ..85 Ion channel blockers...86 IOT-101.........86 Endovion........86 LPAAT-beta inhibitors .86 PARP inhibitors ....87 Targeted destruction of BRCA2 deficient tumors by PARP inhibitors .....87 Prodrugs .............87 Enzyme-activated prodrugs ...87 Ascorbic acid as a prodrug for cancer.....88 Prolarix ..........88 Protein kinase G activation .........88 Proteasome inhibitors .89 Recombinant human insulin-like growth factor binding protein-3........89 Second generation nucleosides ...90 Targeting topoisomerase IB........90 Therapeutic strategies based on the P53 pathway .............91 Development of targeted anticancer therapies ...91 In vivo models for molecularly anticancer drugs...........91 Checkpoint activation as a strategy against cancer .......92 Deletion-specific targeting for cancer therapy ..............92 Combining novel anticancer approaches......92 Personalized therapy of cancer.. 93 Challenges of cancer classification..............96 Design of future cancer therapies96 Personalized drug development in oncology.97 Role of molecular imaging .....97 Role of molecular imaging in targeted cancer therapy ...98 Screening for personalized anticancer drugs .98 Targeting pathways for personalized cancer therapy .....98 3. Drug delivery systems for cancer .... 101 Introduction....... 101 Routes of drug delivery in cancer............ 101 Intravenous delivery systems for cancer therapy............. 102 Oral delivery of anticancer agents ............ 103 Oral UFT ...... 103 5-FU combined with eniluracil ............. 104 Oral paclitaxel..... 105 Oral fluoropyrimidines......... 105 Oral satraplatin ... 106 Oral PXD101. 106 ARRY-142886 ..... 106 High dose pulse administration of calcitrol .. 106 Transdermal drug delivery........ 106 Delivery of the photosensitizer drug d-amino levulinic acid ......... 107 Transdermal delivery of the methotrexate .. 107 Transdermal delivery of peptide cancer vaccines ........ 107 Intradermal delivery of cancer vaccines by adenoviral vectors .... 108 Pulmonary delivery of anticancer agents ... 108 Regional intra-arterial delivery of chemotherapy ............. 108 Gas embolotherapy of tumors... 109 - 6 - Drug delivery to lymph nodes ... 109 Intraperitoneal macrophages as drug delivery vehicle...... 110 Challenges of cancer drug delivery ........... 110 Tumor blood vessel pore barrier to drug delivery............. 110 Improvement of drug transport in tumors . 110 Delivery of anticancer drugs to nuclear targets 111 Innovative formulations for drug delivery in cancer .... 112 Cancer targeting with polymeric drugs ...... 112 Linking anticancer drugs to polyglutamate.. 113 Bacterial ghosts as drug delivery systems for anticancer drugs ........ 113 Microparticles as therapeutic delivery systems in cancer .. 114 Subcutaneous injection of microspheres carrying anticancer drugs .... 114 Intravascular delivery systems using microparticles.... 115 Tumor embolization with drug-eluting beads.............. 115 Tumor embolization with radioactive microparticles .... 116 Microparticles heated by magnetic field 116 Magnetic targeted microparticle technology 116 Release of drugs from micelles by ultrasound ............ 116 Release of drugs from biSphere by ultrasound ........... 117 Release of drugs from microcapsules by laser ............ 117 Chemoembolization ............ 118 Anticancer drugs bound to carbon particles 118 Anticancer drugs bound to protein microspheres ........ 118 Nanoerythrosomes ............. 118 Micronized droplets of olive oil ............ 118 Nanobiotechnology-based drug delivery for cancer ..... 119 Nanoparticle formulations for drug delivery in cancer....... 120 Anticancer drug particles incorporated in liposomes.... 120 Bacterial nanoparticles for encapsulation and chemotherapy delivery. 121 Encapsulating drugs in hydrogel nanoparticles ........... 122 Exosomes .... 122 Folate-linked nanoparticles .. 123 Lipid based nanocarriers ..... 123 Micelles for drug delivery in cancer ...... 123 Nanoparticle formulations of paclitaxel. 125 Nanoparticles containing albumin and antisense oligonucleotides 125 Non-aggregating nanoparticles ........... 125 Pegylated nanoliposomal formulation... 126 Perfluorocarbon nanoparticles............. 126 Protosphere nanoparticle technology ... 126 Nanoparticles for targeted delivery of drugs into the cancer cells ..... 127 Antiangiogenic therapy using nanoparticles 128 Carbon magnetic nanoparticles for targeted drug delivery in cancer... 128 Carbon nanotubes for targeted drug delivery to cancer cells ....... 128 Fullerenes for enhancing tumor targeting by antibodies.............. 129 Gold nanoparticles for drug delivery in cancer............ 129 Iron oxide magnetic nanoparticle formulation for drug delivery ... 130 Lipoprotein nanoparticles targeted to cancer-associated receptors..... 130 Magnetic nanoparticles for remote-controlled drug delivery to tumors 131 Nanocell for targeted drug delivery to tumor.............. 131 Nanodroplets for site-specific cancer treatment.......... 132 Polymer nanoparticles for targeted drug delivery in cancer ......... 132 Polymersomes for targeted cancer drug delivery ........ 133 Targeted drug delivery with nanoparticle-aptamer bioconjugates 133 Dendrimers for anticancer drug delivery.... 134 Application of dendrimers in boron neutron capture therapy ....... 135 Application of dendrimers in photodynamic therapy .... 135 Dendrimer-based synthetic vector for targeted cancer gene therapy.. 136 Devices for nanotechnology-based cancer therapy........... 136 Convection-enhanced delivery with nanoliposomal CPT-11 ......... 136 Nanocomposite devices....... 136 Nanoengineered silicon for brachytherapy .. 137 Nanoparticles combined with physical agents for tumor ablation ...... 137 Carbon nanotubes for laser-induced cancer destruction.............. 137 Nanoparticles and thermal ablation...... 137 Nanoparticles combined with ultrasound radiation of tumors....... 138 Nanoparticles as adjuncts to photodynamic therapy of cancer..... 138 Nanoparticles for boron neutron capture therapy........ 139 RNA nanotechnology for delivery of cancer therapeutics... 139 Nanocarriers for simultaneous delivery of multiple anticancer agents 140 Combination of diagnostics and therapeutics for cancer ... 140 - 7 - Biomimetic nanoparticles targeted to tumors ............. 140 Dendrimer nanoparticles for targeting and imaging tumors......... 140 Gold nanorods for diagnosis plus photothermal therapy of cancer 141 Magnetic nanoparticles for imaging as well as therapy of cancer . 141 pHLIP nanotechnology for detection and targeted therapy of cancer .. 142 Radiolabeled carbon nanotubes for tumor imaging and targeting. 142 Targeted therapy with magnetic nanomaterials guided by antibodies . 142 Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles ............. 142 Polyethylene glycol technology.. 143 Enzon's PEG technology ...... 143 Debiopharm's PEG biconjugate drug delivery platform 143 Nektar PEGylation .............. 144 PEG Intron ... 144 Single-chain antibody-binding protein technology............ 145 Liposomes for anticancer drug delivery ..... 145 AlZA’s Stealth liposomes ..... 147 SkyePharma's DepoFoam .... 147 Hyperthermia and liposomal drug delivery.. 147 Tumor-selective targeted drug delivery via folate-PEG liposomes 148 Boron-containing liposomes. 148 Liposomal doxorubicin formulation with N-octanoyl-glucosylceramide 148 Non-pegilated liposomal doxorubicin.... 149 Emulsion formulations of anticancer drugs ... 149 Albumin-based drug carriers.... 149 Anticancer drugs that bi |
|