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Drug Delivery


Drug Delivery in Cancer

Technologies, Markets and Companies

Publication Date   March 2008
Publisher   Jain PharmaBiotech
Product Type   Strategic Report
Pages   552
ISBN Number   not applicable
Product Code   JAI007
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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 2007-2017 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 193 companies involved in developing innovative cancer therapies and methods of delivery are presented along with their 190 collaborations. The bibliography contains over 580 publications that are cited in the report.The report is supplemented with 53 tables and 7 figures.

Content


  • 0. Executive Summary
  • 1. Introduction to cancer therapy
    • Molecular biology of cancer
    • The genesis of cancer
    • Normal cell cycle and growth
    • Oncogenes
    • Tumor Suppressor Genes
    • Role of microRNAs in cancer
    • Role of Bub 1 gene in cell division
    • Accumulation of random mutations
    • Chromosomal instability
    • Aneuploidy
    • Telomeres and cancer
    • DNA methylation and cancer
    • Anticancer treatments based on RNA regulation of genes
    • Hallmarks of cancer
    • Self-sufficiency of tumor proliferation
    • Apoptosis
    • Therapeutic implications of apoptosis in cancer
    • Autophagy
    • Induction of angiogenesis
    • Acquisition of a potential for unlimited replication
    • Invasion and metastases
    • Cancer biomarkers
    • Molecular imaging of cancer
    • Cancer genomics
    • Gene expression profiling in cancer
    • Cancer proteomics
    • Limitations of genomics and proteomics for understanding cancer
    • Cancer microenvironment
    • Role of hypoxia and miRNA in cancer microenvironment
    • Epidemiology of cancer
    • Current management of cancer
    • Chemotherapy
    • Limitations of cancer chemotherapy
    • Radiotherapy
    • Brachytherapy
    • Surgery
    • Basics of drug delivery in cancer
    • Historical landmarks in cancer drug delivery
  • 2. Innovative treatments for cancer
    • Introduction
    • Selective estrogen receptor modulators
    • Antiangiogenic agents
    • Development of antiangiogenic therapies
    • Classification of antiangiogenic agents
    • Blocking Akt signaling pathway by rapamycin
    • Inhibitors of endothelial proliferation
    • Inducers of apoptosis of endothelial cells of tumor vessels
    • Chemotherapy at lower than maximum tolerated dose
    • Monoclonal antibodies with vasculostatic properties
    • Matrix metalloproteinase inhibitors
    • PPAR? agonists
    • VEGF Trap
    • Agents that decrease the permeability of tumor blood vessels
    • Antiangiogenic agents in clinical trials
    • Combination of antiangiogenic with cytotoxic therapy
    • Bacterial anticancer agents
    • Tumor-targeted bacteria
    • Genetically modified Salmonella typhimurium as anticancer agent
    • TAPET (Tumor Amplified Protein Expression Therapy)
    • Bacterial protein for targeted delivery of liposomal cancer drugs
    • Killed but metabolically active (KBMA) bacteria
    • Bacterial toxins targeted to tumors
    • Immunotoxins
    • Escherichia Coli toxins
    • Engineered anthrax toxin
    • Recombinant fusion toxins
    • Type III secretion systems
    • Induction of apoptosis in cancer by bacterial proteins
    • Induction of immune response by bacteriolytic therapy
    • Innovations in cell therapy for cancer
    • Stem cell transplantation for cancer
    • Cancer drug/gene delivery by mesenchymal stem cells
    • Cancer immunotherapy
    • Cytokines
    • Cancer vaccines
    • 5T4 as a target for cancer immunotherapy
    • Anti-telomerase vaccine
    • Antigen-specific cancer vaccines
    • Carcinoembryonic antigen-based vaccines
    • Dendritic cells for cancer vaccination
    • Hybrid cell vaccination
    • Lymphocyte-based cancer therapies
    • Tumor cell vaccines
    • Vaccines that simultaneously target different cancer antigens
    • Concluding remarks about cancer vaccines
    • Cancer Vaccine Consortium
    • Innovative methods of radiation delivery
    • Image-guided ultrasound technology for delivery of radiation
    • Respiratory gating technology for radiation therapy
    • Positron therapy
    • Boron neutron capture therapy
    • Skeletal Targeted Radiotherapy
    • Irreversible electroporation
    • Methods to overcome multidrug resistance (MDR)
    • P-glycoprotein-mediated MDR
    • MDR-associated protein gene
    • Strategies for overcoming MDR
    • Blocking the action of P-glycoprotein
    • Nitric oxide inducers
    • Managing resistance to antiapoptotic action of anticancer agents
    • Inhibition of DNA repair
    • Liposome formulation of drugs
    • Modification of the chemical structure of the anticancer drug
    • Enzyme Catalyzed Therapeutic Activation
    • Modulation of SPARC expression
    • Iron chelators that overcomes resistance to chemotherapeutics
    • Proton pump inhibitors
    • Combination of targeted drugs with different specificities
    • Targeted cancer therapies
    • Targeting cellular pathways
    • Targeting antigens in virus-associated cancer
    • Targeting HAAH for cancer therapy
    • Targeting mitochondrial membranes
    • Targeting tumor lymphatics
    • Targeting tyrosine kinase receptors
    • Inhibitors of bcr-abl tyrosine kinase
    • Inhibition of multiple tyrosine kinases
    • Inhibitors of ErbB tyrosine kinase
    • Targeting the Hedgehog signaling pathway
    • Targeting oncogenes
    • Targeting miRNA for cancer therapeutics
    • miRNAs as basis of cancer therapeutics
    • Targeting the transferrin receptor-mediated endocytosis pathway
    • Targeting cancer stem cells
    • Targeting glycoproteins
    • Tagging cancer with sugars
    • Anticancer agents based on glycobiology
    • Targeting cell surface glycoproteins
    • Biofusion for targeted cancer therapy
    • Targeted drug delivery of anticancer agents with controlled activation
    • Targeted delivery of anticancer agents with ReCODE technology
    • Enhancing the effects of radiation and chemotherapy
    • Sensitizing agents for chemotherapy
    • Tesmilifene for chemosensitization
    • CoFactor to enhance the efficacy of chemotherapy
    • Enzyme-enhanced chemotherapy
    • Sensitizing agents for radiotherapy
    • IPdR
    • Manipulation of tumor oxygenation
    • Hypoxia-based methods to enhance chemotherapy and radiotherapy
    • Hyperbaric oxygen and radiation
    • HIF-1 antagonists to enhance radiotherapy
    • Nonsteroidal antiinflammatory drugs enhance tumor radiosensitivity
    • ONCONASE as radiosensitivity enhancer
    • Hyperthermia and chemotherapy/radiation therapy
    • Techniques for hyperthermia
    • Trimodality therapy: radiation, chemotherapy, and hyperthermia
    • Photodynamic therapy
    • Novel anticancer agents
    • Anti-EphA2 antibodies
    • Antioxidants
    • Brostallicin
    • Agents disrupting folate metabolism
    • Pemetrexed
    • Cytotoxic ribonucleases
    • DNA hypomethylating agents
    • Histone-based cancer therapy
    • Histone deacetylase inhibitors
    • Modulation of p300/CBP histone acetyltransferase activity
    • Simulation of endogenous histone for anticancer therapy
    • HSP90 inhibitors
    • Ion channel blockers
    • IOT-101
    • Endovion
    • LPAAT-beta inhibitors
    • PARP inhibitors
    • Targeted destruction of BRCA2 deficient tumors by PARP inhibitors
    • Prodrugs
    • Enzyme-activated prodrugs
    • Ascorbic acid as a prodrug for cancer
    • Prolarix
    • Protein kinase G activation
    • Proteasome inhibitors
    • Recombinant human insulin-like growth factor binding protein-3
    • Second generation nucleosides
    • Targeting topoisomerase IB
    • Therapeutic strategies based on the P53 pathway
    • Development of targeted anticancer therapies
    • In vivo models for molecularly anticancer drugs
    • Checkpoint activation as a strategy against cancer
    • Deletion-specific targeting for cancer therapy
    • Combining novel anticancer approaches
    • Personalized therapy of cancer
    • Challenges of cancer classification
    • Design of future cancer therapies
    • Personalized drug development in oncology
    • Role of molecular imaging
    • Role of molecular imaging in targeted cancer therapy
    • Screening for personalized anticancer drugs
    • Targeting pathways for personalized cancer therapy
  • 3. Drug delivery systems for cancer
    • Introduction
    • Routes of drug delivery in cancer
    • Intravenous delivery systems for cancer therapy
    • Oral delivery of anticancer agents
    • Oral UFT
    • 5-FU combined with eniluracil
    • Oral paclitaxel
    • Oral fluoropyrimidines
    • Oral satraplatin
    • Oral PXD101
    • ARRY-142886
    • High dose pulse administration of calcitrol
    • Transdermal drug delivery
    • Delivery of the photosensitizer drug d-amino levulinic acid
    • Transdermal delivery of the methotrexate
    • Transdermal delivery of peptide cancer vaccines
    • Intradermal delivery of cancer vaccines by adenoviral vectors
    • Pulmonary delivery of anticancer agents
    • Regional intra-arterial delivery of chemotherapy
    • Gas embolotherapy of tumors
    • Drug delivery to lymph nodes
    • Intraperitoneal macrophages as drug delivery vehicle
    • Challenges of cancer drug delivery
    • Tumor blood vessel pore barrier to drug delivery
    • Improvement of drug transport in tumors
    • Delivery of anticancer drugs to nuclear targets
    • Innovative formulations for drug delivery in cancer
    • Cancer targeting with polymeric drugs
    • Linking anticancer drugs to polyglutamate
    • Bacterial ghosts as drug delivery systems for anticancer drugs
    • Microparticles as therapeutic delivery systems in cancer
    • Subcutaneous injection of microspheres carrying anticancer drugs
    • Intravascular delivery systems using microparticles
    • Tumor embolization with drug-eluting beads
    • Tumor embolization with radioactive microparticles
    • Microparticles heated by magnetic field
    • Magnetic targeted microparticle technology
    • Release of drugs from micelles by ultrasound
    • Release of drugs from biSphere by ultrasound
    • Release of drugs from microcapsules by laser
    • Chemoembolization
    • Anticancer drugs bound to carbon particles
    • Anticancer drugs bound to protein microspheres
    • Nanoerythrosomes
    • Micronized droplets of olive oil
    • Nanobiotechnology-based drug delivery for cancer
    • Nanoparticle formulations for drug delivery in cancer
    • Anticancer drug particles incorporated in liposomes
    • Bacterial nanoparticles for encapsulation and chemotherapy delivery
    • Encapsulating drugs in hydrogel nanoparticles
    • Exosomes
    • Folate-linked nanoparticles
    • Lipid based nanocarriers
    • Micelles for drug delivery in cancer
    • Nanoparticle formulations of paclitaxel
    • Nanoparticles containing albumin and antisense oligonucleotides
    • Non-aggregating nanoparticles
    • Pegylated nanoliposomal formulation
    • Perfluorocarbon nanoparticles
    • Protosphere nanoparticle technology
    • Nanoparticles for targeted delivery of drugs into the cancer cells
    • Antiangiogenic therapy using nanoparticles
    • Carbon magnetic nanoparticles for targeted drug delivery in cancer
    • Carbon nanotubes for targeted drug delivery to cancer cells
    • Fullerenes for enhancing tumor targeting by antibodies
    • Gold nanoparticles for drug delivery in cancer
    • Iron oxide magnetic nanoparticle formulation for drug delivery
    • Lipoprotein nanoparticles targeted to cancer-associated receptors
    • Magnetic nanoparticles for remote-controlled drug delivery to tumors
    • Nanocell for targeted drug delivery to tumor
    • Nanodroplets for site-specific cancer treatment
    • Polymer nanoparticles for targeted drug delivery in cancer
    • Polymersomes for targeted cancer drug delivery
    • Targeted drug delivery with nanoparticle-aptamer bioconjugates
    • Dendrimers for anticancer drug delivery
    • Application of dendrimers in boron neutron capture therapy
    • Application of dendrimers in photodynamic therapy
    • Dendrimer-based synthetic vector for targeted cancer gene therapy
    • Devices for nanotechnology-based cancer therapy
    • Convection-enhanced delivery with nanoliposomal CPT-11
    • Nanocomposite devices
    • Nanoengineered silicon for brachytherapy
    • Nanoparticles combined with physical agents for tumor ablation
    • Carbon nanotubes for laser-induced cancer destruction
    • Nanoparticles and thermal ablation
    • Nanoparticles combined with ultrasound radiation of tumors
    • Nanoparticles as adjuncts to photodynamic therapy of cancer
    • Nanoparticles for boron neutron capture therapy
    • RNA nanotechnology for delivery of cancer therapeutics
    • Nanocarriers for simultaneous delivery of multiple anticancer agents
    • Combination of diagnostics and therapeutics for cancer
    • Biomimetic nanoparticles targeted to tumors
    • Dendrimer nanoparticles for targeting and imaging tumors
    • Gold nanorods for diagnosis plus photothermal therapy of cancer
    • Magnetic nanoparticles for imaging as well as therapy of cancer
    • pHLIP nanotechnology for detection and targeted therapy of cancer
    • Radiolabeled carbon nanotubes for tumor imaging and targeting
    • Targeted therapy with magnetic nanomaterials guided by antibodies
    • Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles
    • Polyethylene glycol technology
    • Enzon's PEG technology
    • Debiopharm's PEG biconjugate drug delivery platform
    • Nektar PEGylation
    • PEG Intron
    • Single-chain antibody-binding protein technology
    • Liposomes for anticancer drug delivery
    • Antibody-targeted liposomes for cancer therapy
    • AlZA's Stealth liposomes
    • Boron-containing liposomes
    • DepoFoam technology
    • Hyperthermia and liposomal drug delivery
    • Liposomal doxorubicin formulation with N-octanoyl-glucosylceramide
    • Non-pegilated liposomal doxorubicin
    • Tumor-selective targeted drug delivery via folate-PEG liposomes
    • Companies developing liposome-based anticancer drugs
    • Emulsion formulations of anticancer drugs
    • Albumin-based drug carriers
    • Anticancer drugs that bind to tumors
    • Monoclonal antibodies
    • Murine monoclonal antibodies
    • Humanized MAbs
    • Actions and uses of monoclonal antibodies in cancer
    • Anti-Thomsen-Friedenreich antigen MAb
    • MAbs targeted to alpha fetaprotein receptor
    • MAbs targeted to cell surface proteins
    • MAbs targeted to tumor blood vessels
    • MAbs targeted to HAAH
    • MAbs for immune activation
    • Facilitating action of MAbs by combination with anti-CD55 antibody
    • Delivery of cancer therapy with MAbs
    • Antibody-directed enzyme prodrug therapy
    • Antibody J591 for targeted delivery of anticancer therapy
    • Chemically programmed antibodies
    • Combining diagnostics with therapeutics based on MAbs
    • Radiolabeled antibodies
    • Clinical development of MAbs for treatment of cancer
    • Advantages and limitations of MAbs for cancer therapy
    • Monoclonal T cell receptors
    • Radiolabeled somatostatin receptor antagonists
    • Strategies for drug delivery in cancer
    • Direct introduction of anticancer drugs into the tumor
    • Injection into the tumor
    • Antineoplastic drug implants into tumors
    • Tumor necrosis therapy
    • Injection into the arterial blood supply of cancer
    • Electrochemotherapy
    • Pressure-induced filtration of drugs across vessels to the tumor
    • Improving drug transport to tumors
    • Carbohydrate-enhanced chemotherapy
    • Dextrans as macromolecular anticancer drug carriers
    • In situ production of anticancer agents in tumors
    • Targeted drug delivery in cancer
    • Affibody molecules for targeted anticancer therapy
    • Fatty acids as targeting vectors
    • Genetic targeting of the kinase activity in cancer cells
    • Heat-activated targeted drug delivery
    • Novel transporters to target photosensitizers to cancer cell nuclei
    • Photodynamic therapy of cancer
    • Targeting ligands specific for cancer cells
    • Targeting abnormal DNA in cancer cells
    • Targeting using a bispecific antibody
    • Targeted chemotherapy using transporters
    • Targeted generation of intracellular reactive oxygen species
    • Targeted cytotoxic peptides
    • Targeted delivery to receptors found in tumors
    • Targeted delivery by tumor-activated prodrug therapy
    • Targeting glutathione S-transferase
    • Targeting tumors by exploiting leaky blood vessels
    • Transmembrane Carrier Systems
    • Transferrin-oligomers as targeting carriers in anticancer drug delivery
    • Ultrasound for targeted anticancer drug delivery
    • Vitamin B12 and folate for targeting cancer chemotherapy
    • Drug delivery in relation to circadian rhythms
    • Implants for systemic delivery of anticancer drugs
    • Angiogenesis and drug delivery to tumors
    • Antiangiogenesis strategies
    • Targeting tumor endothelial cells
    • Methods for overcoming limitations of antiangiogenesis approaches
    • Vascular targeting agents
    • Alpha-emitting antibodies for vascular targeting
    • Angiolytic therapy
    • Anti-phosphatidylserine antibodies as VTA
    • AS1404
    • Cadherin inhibitors
    • Combretastatin A4 Prodrug
    • Drugs to induce clotting in tumor vessels
    • Selective permeation of the anticancer agent into the tumor
    • Targeted delivery of tissue factor
    • Vascular targeting agents versus antiangiogenesis agents
    • ZD6126
    • Delivery of proteins and peptides for cancer therapy
    • CELLECTRA electroporation device
    • Emisphere's eligen system
    • Diatos Peptide Vector intra-cellular/intra-nuclear delivery technology
    • Lytic peptides and cancer
    • Modification of proteins and peptides with polymers
    • Peptide-based targeting of cancer biomarkers for drug delivery
    • Peptide-polymer conjugates with radionuclides
    • Transduction of proteins in vivo
    • Tumor targeting by stable toxin (ST) peptides
    • Cell-based cancer vaccines
    • Autologous tumor cell vaccines
    • Vaccines that simultaneously target different cancer antigens
    • Delivery systems for cancer vaccines
    • A computational approach to integration of drug delivery methods for cancer
  • 4. Antisense, RNAi and Gene Therapy for Cancer
    • Basics of antisense therapy
    • Antisense cancer therapy
    • Mechanisms of anticancer effect of antisense oligonucleotides
    • Selected antisense drugs in development for cancer
    • Antisense targeted to ribonucleotide reductase
    • Targeting C-myb with LR3001
    • Immune modulatory oligonucleotide
    • Ribozyme therapy
    • Antisense drug delivery issues
    • Strategies to overcome delivery problems of antisense oligonucleotides
    • Oral delivery of oligonucleotides
    • Iontophoretic delivery of oligonucleotides
    • Delivery across the blood-brain barrier
    • Receptor-mediated endocytosis
    • Liposomes-mediated oligonucleotide delivery
    • Antisense delivery in microspheres
    • Antisense nanoparticles
    • Peptide nucleic acid delivery
    • Neugene? antisense drugs
    • Delivery of ribozymes
    • Combination of antisense and electrochemotherapy
    • Aptamers for combined diagnosis and therapeutics of cancer
    • Antisense and RNAi
    • Basics of RNAi
    • Comparison of antisense and RNAi
    • RNAi applications in oncology
    • Delivery of siRNA by nanoparticles
    • Delivery of siRNA by nanosize liposomes
    • Calando's technology for targeted delivery of anticancer siRNA
    • Companies developing cancer therapies based on antisense and RNAi
    • DNA interference
    • Cancer gene therapy
    • Basics of gene therapy
    • Strategies for cancer gene therapy
    • Gene transfer techniques as applied to cancer gene therapy
    • Viral vectors
    • Non-viral vectors
    • A polymer approach to gene therapy for cancer
    • Direct gene delivery to the tumor
    • Injection into tumor
    • Reversible electroporation
    • Hematopoietic gene transfer
    • Genetic modification of human hematopoietic stem cells
    • Gene-based strategies for immunotherapy of cancer (immunogene therapy)
    • Cytokine gene therapy
    • Nucleic acid-based cancer vaccines
    • DNA cancer vaccines
    • Methods of delivery of DNA vaccines
    • RNA vaccines
    • Viral vector-based cancer vaccines
    • Genetically modified cancer cells vaccines
    • GVAX cancer vaccines
    • Genetically modified dendritic cells
    • Use of hematopoietic stem cells for targeted cancer therapy
    • Companies involved in nucleic acid-based vaccines
    • Monoclonal antibody gene transfer
    • Transfer and expression of intracellular adhesion-1 molecules
    • Other gene-based techniques of immunotherapy of cancer
    • Fas (Apo-1)
    • Chemokines
    • Major Histocompatibility Complex (MHC) Class I
    • IGF (Insulin-Like Growth Factor)
    • Inhibition of immunosuppressive function
    • Delivery of toxic genes to tumor cells for eradication (molecular chemotherapy)
    • Gene-directed enzyme prodrug therapy
    • Combination of gene therapy with radiotherapy
    • Multipronged therapy of cancer with microencapsulated cells
    • Correction of genetic defects in cancer cells (mutation compensation)
    • Targeted gene therapy for cancer
    • Transcriptional targeting for cancer gene therapy
    • Targeted epidermal growth factor-mediated DNA delivery
    • Gene-based targeted drug delivery to tumors
    • Targeting gene expression to hypoxic tumor cells
    • Targeting gene expression by progression-elevated gene-3 promoter
    • Targeted delivery of retroviral particles hitchhiking on T cells
    • Targeting tumors with genetically modified T cells
    • Targeting tumors by genetically engineered stem cells
    • Tumor-targeted gene therapy by receptor-mediated endocytosis
    • Targeted site-specific delivery of anticancer genes by nanoparticles
    • Immunolipoplex for delivery of p53 gene
    • Combination of electrogene and electrochemotherapy
    • Virus-mediated oncolysis
    • Targeted cancer treatments based on oncolytic viruses
    • Oncolytic gene therapy
    • Cytokine-induced killer cells for delivery of an oncolytic virus
    • Oncolytic HSV
    • Oncolytic adenoviruses
    • Oncolytic vesicular stomatitis virus
    • Oncolytic measles virus
    • Oncolytic paramyxovirus
    • Oncolytic reovirus
    • Oncolytic vaccinia virus
    • Cancer terminator virus
    • Monitoring of viral-mediated oncolysis by PET
    • Companies developing oncolytic viruses
    • Bacteria as novel anticancer gene vectors
    • Apoptotic approach to improve cancer gene therapy
    • Concluding remarks on cancer gene therapy
    • Cancer gene therapy companies
  • 5. Delivery strategies according to cancer type and location
    • Introduction
    • Bladder cancer
    • Intravesical drug delivery
    • Intravesical agents combined with systemic chemotherapy
    • Targeted anticancer therapy for bladder cancer
    • Prodrug EOquin for bladder cancer
    • Antisense treatment of bladder cancer
    • Gene therapy for bladder cancer
    • Brain tumors
    • Anticancer agents with increased penetration of BBB
    • Combination of chemotherapy with radiotherapy
    • Local delivery of chemotherapeutic agents into the tumor
    • Carmustine biodegradable polymer implants
    • Fibrin glue implants containing anticancer drugs
    • Biodegradable microspheres containing 5-FU
    • Magnetically controlled microspheres
    • Convection-enhanced delivery
    • Receptor-directed cytotoxin therapy
    • Delivery of a modified diphtheria toxin conjugated to transferrin
    • Convection-enhanced delivery with nanoliposomal CPT-11
    • Monoclonal antibodies targeted to brain tumors
    • Use of nanoparticles for drug delivery in glioblastoma multiforme
    • Targeted delivery of nanoparticles to tumors
    • Immunoliposomes
    • Lipid-coated microbubbles as a delivery vehicle for taxol
    • Thermoliposomes containing cytotoxic drugs
    • Targeted antiangiogenic/apoptotic/cytotoxic therapies for brain tumors
    • Multiple targeted drugs for brain tumors
    • Introduction of the chemotherapeutic agent into the CSF pathways
    • Intraventricular chemotherapy for meningeal cancer
    • Intrathecal chemotherapy
    • Increasing the permeability of blood-tumor barrier to anticancer drugs
    • BBB disruption
    • Tyrosine kinase inhibitor increases topotecan penetration into CNS
    • Intra-arterial chemotherapy
    • Interstitial delivery of dexamethasone for reduction of peritumor edema
    • Photodynamic therapy for chemosensitization of brain tumors
    • Nanoparticles for photodynamic therapy of brain tumors
    • Innovative delivery of radiotherapy to brain tumors
    • GliaSite Radiation Therapy System
    • Boron neutron capture therapy for brain tumors
    • Cell therapy for glioblastoma multiforme
    • Mesenchymal stem cells to deliver treatment for gliomas
    • Gene therapy for glioblastoma multiforme
    • Single-chain antibody-targeted adenoviral vectors
    • Intravenous gene delivery with nanoparticles into brain tumors
    • Neural stem cells for drug/gene delivery to brain tumors
    • Peptides targeted to glial tumor cells
    • Treatment of medulloblastoma by suppressing genes in Shh pathway
    • Antiangiogenic gene therapy
    • Anticancer drug delivery by genetically engineered MSCs
    • RNAi gene therapy of brain cancer
    • Ligand-directed delivery of dsRNA molecules targeted to EGFR
    • Virus-mediated oncolytic therapy of brain cancer
    • Breast Cancer
    • Combination targeted treatment stops breast cancer growth
    • Therapies for breast cancer involving innovative methods of drug delivery
    • Injectable biodegradable polymer delivery system for local chemotherapy
    • MammoSite brachytherapy
    • Monoclonal antibodies for breast cancer
    • Breast cancer vaccines
    • HER-2 DNA AutoVac? vaccine
    • Gene vaccine for breast cancer
    • Gene therapy for breast cancer
    • Intratumoral injection of Ad5CMV-p53
    • Antisense therapy for breast cancer
    • Inhibitors of growth factors FGF2 and VEGF
    • Drug delivery for cancer of the cervix and the uterus
    • Gene therapy for cervical cancer
    • Delivery of chemoradiation therapy
    • Cervical cancer vaccines
    • Leukemia
    • Clofarabine
    • Malignant melanoma
    • Targeted therapies for melanoma
    • Immunotherapy for malignant melanoma
    • Gene therapy for malignant melanoma
    • Neuroblastoma
    • Genetically modified NSCs for treatment of neuroblastoma
    • Non-small cell lung cancer
    • Intratumoral administration of anticancer drugs through a bronchoscope
    • Aerosol delivery of anticancer agents for lung cancer
    • Aerosol gene delivery for lung cancer
    • Ovarian cancer
    • Innovative drug delivery for ovarian cancer
    • Intraperitoneal delivery
    • Gene Therapy for ovarian cancer
    • Pancreatic cancer
    • Targeted chemotherapy for pancreatic cancer
    • Local anticancer drug delivery for pancreatic cancer
    • Vaccine for pancreatic cancer
    • Gene therapy for pancreatic cancer
    • Adenovirus-mediated transfer of vasostatin gene
    • Rexin-G? for targeted gene delivery in pancreatic cancer
    • Targeted Expression of BikDD gene
    • Prostate cancer
    • PACLIMER Microspheres
    • PRX302
    • Brachytherapy for cancer of prostate
    • Capridine-beta
    • LHRH for prostate cancer
    • LHRH analogs
    • Histrelin implant
    • Immunomodulatory drugs
    • MAbs for prostate cancer
    • Targeted therapies for prostate cancer
    • Delivery of siRNAs to prostate cancer with aptamer-siRNA chimeras
    • Delivery of siRNA for prostate cancer with metastases
    • Nanoparticulate delivery of suicide DNA to prostate tumors
    • PSA-activated protoxin that kills prostate cancer
    • Targeted drug delivery with nanoparticle-aptamer bioconjugates
    • Targeting oncogene MDM2 in prostate cancer
    • Vascular targeting of prostate cancer
    • Gene therapy for cancer of prostate
    • Experimental studies
    • Tumor suppressor gene therapy in prostate cancer
    • Clinical trials
    • Combined approaches
    • Combined autovaccination and hyperthermia
    • Hepatocellular carcinoma
  • 6. Cancer drug delivery markets
    • Introduction
    • Global markets for drug delivery
    • Estimation of cancer drug delivery markets
    • Methods used for market estimation
    • Cancer epidemiology
    • Cost of patient care in cancer
    • Market forecasts 2007-2017
    • Cancer drug market
    • Markets for leukemia
    • Markets for brain tumors
    • Geographical distribution of cancer markets
    • Factors affecting future cancer markets
    • Market share according to cancer drug delivery technologies
    • Antiangiogenesis therapies
    • Antineoplastic drug implants for systemic administration
    • Antisense therapy and RNAi
    • Cancer vaccines
    • Gene therapy
    • Liposomes for anticancer drugs
    • Monoclonal antibodies
    • Strategic aspects of cancer drug delivery
    • Unmet needs in cancer drug delivery
    • Future prospects of cancer drug delivery
    • Cancer drug delivery and pharmacogenomics
    • Drug delivery for cancer in the postgenomic era
    • Role of nanobiotechnology in development of cancer drug delivery markets
    • Expansion of cancer drug delivery markets in developing countries
    • Drivers for the development of drug delivery technologies in cancer
  • 7. References
  • Tables
    • Table 1 1: Estimated new cases of cancer in the US at most involved organs ? 2007
    • Table 1 2: Historical landmarks in drug delivery for cancer
    • Table 2 1: Innovative strategies against cancer
    • Table 2 2: A classification of antiangiogenic therapies
    • Table 2 3: Antiangiogenic agents in clinical trials
    • Table 2 4:Approaches to cancer therapy based on bacteria
    • Table 2 5: Cell therapy technologies used for cancer
    • Table 2 6: Non-nucleic acid cancer vaccines without genetic modification
    • Table 2 7: Cellular pathways as targets for anticancer therapies
    • Table 2 8: Examples of anticancer agents that target mitochondrial membranes
    • Table 2 9: Drugs targeting oncogenes
    • Table 2 10: Cancer therapies based on the P53 pathway
    • Table 2 11: Promise of personalized therapy in cancer
    • Table 2 12: Companies developing personalized therapy for cancer
    • Table 3 1: Routes of drug delivery in cancer
    • Table 3 2: Systemic intravenous drug delivery systems for chemotherapy of cancer
    • Table 3 3: Microparticles as therapeutic delivery systems in cancer
    • Table 3 4: Classification of nanobiotechnology approaches to drug delivery in cancer
    • Table 3 5: Liposome-based anticancer drug delivery
    • Table 3 6: Approved monoclonal antibodies for cancer
    • Table 3 7: Anticancer agents linked to monoclonal antibodies
    • Table 3 8: Monoclonal antibodies in clinical trials for cancer
    • Table 3 9: Strategies for drug delivery in cancer
    • Table 3 10: Implant systems for delivery of anticancer drugs into tumors
    • Table 3 11: Systemic delivery of drugs targeted to the tumor
    • Table 3 12: Methods of delivery of antiangiogenesis therapies
    • Table 3 13: Companies developing vascular targeting agents
    • Table 4 1: Mechanisms of anticancer effect of antisense oligonucleotides
    • Table 4 2: Methods of delivery of oligonucleotides for cancer therapy
    • Table 4 3: Companies developing antisense and RNAi therapies for cancer
    • Table 4 4: Strategies for cancer gene therapy
    • Table 4 5: Companies developing nucleic acids/genetically modified cells-based cancer vaccines
    • Table 4 6: Enzyme/prodrug combinations employed in suicide gene therapy
    • Table 4 7: Mutation compensation strategies used clinically
    • Table 4 8: Companies developing oncolytic viruses
    • Table 4 9: Companies involved in cancer gene therapy
    • Table 5 1: Innovative methods of drug delivery for glioblastoma multiforme
    • Table 5 2: Strategies for gene therapy of malignant brain tumors
    • Table 5 3: Therapies for breast cancer involving innovative methods of drug delivery
    • Table 5 4: Gene therapy for malignant melanoma
    • Table 5 5: Targeted treatment of non-small-cell lung cancer
    • Table 5 6: Clinical trials of gene therapy in ovarian cancer
    • Table 5 7: Methods of drug delivery in pancreatic cancer
    • Table 5 8: Pharmacological strategies under investigation for cancer of the prostate
    • Table 5 9: Recent clinical trials in gene therapy for prostate cancer
    • Table 5 10: Drug delivery for hepatocellular carcinoma
    • Table 6 1: Worldwide drug delivery market growth 2007 to 2017
    • Table 6 2: Estimated worldwide prevalence of cancer according to type of cancer
    • Table 6 3: Estimated number of cancer patients in major markets 2007-2017
    • Table 6 4: Worldwide values for therapies of selected cancers from 2007 to 2017
    • Table 6 5: Geographical distribution of cancer markets 2007-2017
    • Table 6 6: Market values of cancer drug delivery technologies from 2007-2017
  • Figures
    • Figure 1 1: An overview of some key steps in tumor angiogenesis
    • Figure 2 1: Schematic role of T-helper cells in immune response to cancer
    • Figure 3 1: Cyclacel's Penetratin Transport System for delivery of drugs to targets
    • Figure 3 2: Micelle for drug delivery in cancer
    • Figure 3 3: Mechanism of action of Targaceutical drugs
    • Figure 3 4: ALZA's DUROS implant
    • Figure 6 1: Unmet needs in cancer drug delivery"