Drug Delivery in Cancer - Technologies, Markets & Companies

Table of Contents

Part I: Technologies and Markets

0. Executive Summary

1. Introduction to cancer therapy

• Molecular biology of cancer
• Cell cycle and cancer
• Apoptosis in cancer
• Autophagy
• Cell division and mitotic spindles
• PD-1 Pathway
• DNA damage, repair and cancer
• Mechanism of DNA damage in Fanconi anemia leading to leukemia
• Cancer metabolism and energy status in relation to growth
• Amino acids and cancer
• AMP-activated protein kinase
• Cancer therapeutics that target metabolism.
• Cancer cell dormancy
• Dormancy and relapse in cancer
• Activating dormant cancer cells for enhancing chemotherapy
• Chromosomes and cancer
• Aneuploidy
• Chromosomal instability
• Chromothripsis
• Extrachromosomal DNA and cancer
• Telomeres and cancer
• Genes and cancer
• Accumulation of random mutations
• Oncogenes
• Role of Bub 1 gene in cell division
• Tumor Suppressor Genes
• Hallmarks of cancer
• Hypoxia of cancer cells
• Invasion and metastases
• Tumor suppressor genes and metastases
• Methylation and cancer
• Nitric oxide and cancer
• Inflammation, NO and colon cancer
• NO and tumor hypoxia
• NO and p53 mutations
• NO and matrix metalloproteinase
• Role of NO in angiogenesis in cancer
• Oxidative stress and cancer
• Role of platelet-derived growth factor in proliferation of cancer
• RNA and cancer
• Anticancer treatments based on RNA regulation of genes
• Role of microRNAs in cancer
• Stem cells and cancer
• Self-sufficiency of tumor proliferation
• Therapeutic implications of apoptosis in cancer
• Tumor angiogenesis
• Pathomechanism of angiogenesis
• Role of VEGF in angiogenesis
• Matrix stiffness-mediated angiogenesis in tumors
• Tumor-associated macrophages in cancer
• 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
• Epidemiology of cancer
• Current management of cancer
• Anticancer drugs
• Limitations of cancer chemotherapy
• Biological therapies for cancer
• Radiotherapy
• Brachytherapy
• Ideal anticancer agent
• Surgery
• Basics of drug delivery in cancer
• Role of mechanical forces in tumor growth and delivery of therapy
• Methods of assessing drug delivery in cancer
• Positron emission tomography (PET)
• Historical landmarks in cancer drug delivery

2. Innovative treatments for cancer

• Introduction
• Selective estrogen receptor modulators
• Antiangiogenic strategies for cancer
• Development of antiangiogenic therapies
• Classification of antiangiogenic agents
• Examples of antiangiogenic agents
• ACE-041
• Angiopoietin-2 as a target
• Chemotherapy at lower than maximum tolerated dose
• Galectin-3 as a target for inhibiting angiogenesis
• Inhibitors of endothelial proliferation
• Inducers of apoptosis of endothelial cells of tumor vessels
• Lodamin
• Matrix metalloproteinase inhibitors
• Monoclonal antibodies with vasculostatic properties
• PPAR agonists
• Rapalogues as antiangiogenic agents
• VEGF Trap
• Agents that decrease the permeability of tumor blood vessels
• Antiangiogenic agents in clinical trials
• Antiangiogenic therapy resistance
• Combination of antiangiogenic with cytotoxic therapy
• Antiangiogenic therapy for hematological malignancies
• Bacterial anticancer agents
• Tumor-targeted bacteria
• Bacterial protein for targeted delivery of liposomal cancer drugs
• Bacterial carriers for targeted drug delivery to brain tumors
• Genetically modified bacteria as anticancer agents
• Live bacteria for delivering radioactive anticancer agents
• Synchronized cycles of bacterial lysis with delivery of chemotherapy
• Genetically altered strains of Salmonella as anticancer drug vectors
• Inactivated but metabolically active 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
• Epigenetic targets for anticancer therapy
• Innovations in cell therapy for cancer
• Stem cell transplantation for cancer
• Cancer drug/gene delivery by mesenchymal stem cells
• 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
• Cancer immunotherapy
• Role of biomarkers in personalized immuno-oncology
• Role of organoids in predicting response to immuno-therapeutic drugs
• Role of tumor-on-chips in immuno-oncology
• Role of molecular diagnostics and sequencing in immuno-oncology
• Genomic testing
• Gene expression signatures
• Personalizing immuno-oncology
• Factors that drive the development of personalized immunotherapy for cancer
• Computational methods for personalized immuno-oncology
• Immune checkpoint inhibitors for cancer
• Checkpoint inhibitors blocking PD-1 or PD-L1
• Antibody blocking the cytotoxic T-lymphocyte-associated protein 4
• Prediction of response to anti-PD-1/PD-L1 therapy in cancer
• Checkpoint inhibitors other than anti-PD-L1
• Personalizing immune checkpoint inhibitor therapy
• Cell-based immune therapies
• Treatments for cancer by ex vivo mobilization of immune cells
• Granulocytes as anticancer agents
• Neutrophil granulocytes in MAb-based immunotherapy of cancer
• Adoptive cell transfer
• Chimeric antigen receptor T cells
• Cytokines
• Cancer vaccines
• Adoptive cell therapy
• Antigen-specific cancer vaccines
• Carcinoembryonic antigen-based vaccines
• Carbohydrate-based cancer vaccines
• Dendritic cells for cancer vaccination
• Hybrid cell vaccination
• SMART vaccines
• Salmonella-based oral vaccine delivery
• Tumor cell vaccines
• Vaccines that simultaneously target different cancer antigens
• Vaccines based on multiple tumor-associated peptides
• Vaccine for cancer based on antimalaria protein
• Cancer Vaccine Consortium
• Personalized cancer vaccines
• Autologous tumor cell vaccines
• DC-based cancer vaccines
• Cytokines as vaccine adjuvants
• Limitations of cancer vaccination
• Role of neoantigens in personalizing cancer vaccines
• Delivery of cancer immunotherapy
• Nanoparticles for delivery of immunotherapy combined with photodynamic therapy
• Synthetic bacteria for local tumor delivery of checkpoint blockade nanobodies
• Transdermal cold atmospheric plasma mediated ICI therapy
• Combination of immunotherapies for cancer
• Epigenetic modulators and cancer immunotherapies
• STING activation and antitumor immunity
• Chemoimmunotherapy
• Concluding remarks about cancer vaccines
• Targeted delivery of peptides to tumor-associated macrophages
• Targeting cancer stem cells
• Concluding remarks and future of personalized immuno-oncology
• Monoclonal antibodies
• Murine MAbs
• Humanized MAbs
• Actions and uses of MAbs in cancer
• Targeted antibody-based cancer therapy
• Antibody–cytokine fusion proteins
• Antibody ARGX-115 for targeting immunosuppressive effect of Tregs
• Anti-Thomsen-Friedenreich antigen MAb
• Combining MAbs with anti-CD55 antibody
• MAbs targeted to alpha fetaprotein receptor
• MAbs that target angiogenesis
• MAbs as phagocyte checkpoint inhibitors
• MAbs for immune activation
• Delivery of cancer therapy with MAbs
• Antibody-directed enzyme prodrug therapy
• Chemically programmed antibodies
• Combining diagnostics with therapeutics based on MAbs
• Radiolabeled antibodies for detection and targeted therapy of cancer
• Other innovations for administration of antibodies
• Bispecific antibodies
• Trifunctional antibodies
• Tetravalent bispecific antibodies
• Immunotoxins
• Immunoliposomes
• Combined use of MAbs and cytokines
• huHMFG1-huDNase I
• MAbs that selectively target cancer
• G-MAB technology
• NanoMAbs for targeted anticancer drug delivery
• Advantages and limitations of MAbs for cancer therapy
• Monoclonal antibodies for personalized management of cancer
• Antibody-drug conjugates
• Kadcyla
• Adcetris
• Antibody-drug conjugates for personalized therapy of cancer
• Antibody-enzyme conjugates
• Current and future trends in antibody-based cancer drugs
• 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
• Application of drug delivery systems to BNCP
• Use of nanotechnology to enhance BNCT
• Ion channels and transporters in cancer
• Irreversible electroporation
• Methods to overcome multidrug resistance (MDR)
• Mechanism of MDR
• MDR-associated protein gene
• P-glycoprotein-mediated MDR
• Strategies for overcoming MDR
• Blocking the action of P-glycoprotein
• Combination of targeted drugs with different specificities
• Enzyme Catalyzed Therapeutic Activation
• Inhibition of DNA repair
• Iron chelators that overcomes resistance to chemotherapeutics
• Liposome formulation of anticancer drugs
• Modification of the chemical structure of the anticancer drug
• Managing resistance to antiapoptotic action of anticancer agents
• Modulation of SPARC expression
• Nanoparticles for producing reactive oxygen species in mitochondria
• Nitric oxide inducers
• Proton pump inhibitors
• Repression of Prohibitin1 in drug-resistant cancer cells
• Targeting proteins associated with cancer stem cells
• Targeted cancer therapies
• Targeting cellular pathways
• Targeting antigens in virus-associated cancer
• Targeting the IGF-I receptor
• Targeting Mcl-1 protein
• Targeting mitochondrial membranes
• Targeting tumor lymphatics
• LyP-1 for 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 caspase-8
• Targeting metallodrugs to tumor cells
• Targeting oncogenes
• Targeting miRNA for cancer therapeutics
• Targeting the transferrin receptor-mediated endocytosis pathway
• Targeted anticancer therapies based on the Rad51 promoter
• Targeting cancer stem cells
• Targeting glycolytic pathway in cancer
• Targeting glycoproteins
• Tagging cancer with modified sugars
• Anticancer agents based on glycobiology
• Targeting cell surface glycoproteins
• Biofusion for targeted cancer therapy
• Targeting knottin peptides
• Tarveda’s Pentarin platform for targeted drug conjugates
• Enhancing the effects of radiation and chemotherapy
• Sensitizing and enhancing agents for chemotherapy
• CoFactor to enhance the efficacy of chemotherapy
• Enzyme-enhanced chemotherapy
• Resveratrol and quercetin for cardioprotection against chemotherapy
• Tesmilifene for chemosensitization
• Sensitizing agents for radiotherapy
• IPdR
• Ultrasound for enhancing response to radiation
• 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
• Photochemical internalization
• Thermal combination with focused ultrasound for drug delivery to tumors
• Novel anticancer agents
• Anti-EphA2 antibodies
• Antioxidants
• Brostallicin
• Agents disrupting folate metabolism
• Pemetrexed
• Cell cycle inhibitors
• 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-β inhibitors
• Modulation of pyruvate kinase M2
• Modulators of protein ubiquitination
• P13-kinase inhibitors
• PARP inhibitors
• Targeted destruction of BRCA2 deficient tumors by PARP inhibitors
• Companies developing and commercializing PARP inhibitors
• Prodrugs
• Enzyme-activated prodrugs
• Ascorbic acid as a prodrug for cancer
• Prolarix
• Procaspase-3 activation
• Protein kinase G activation
• Proteasome inhibitors
• Recombinant human insulin-like growth factor binding protein-3
• Second generation nucleosides
• Targeting cancer metabolism
• Targeting topoisomerase IB
• Telomerase inhibitors
• Therapeutic strategies based on the P53 pathway
• Therapeutic strategies based on molecular mechanisms
• Checkpoint activation as a strategy against cancer
• Deletion-specific targeting for cancer therapy
• In vivo models for molecularly anticancer drugs
• Repair-blocking drugs for enhancing effect of chemotherapy
• Tumor targeting fields
• Targeting mTOR signaling defects
• Combining novel anticancer approaches
• Personalized therapy of cancer
• Promise of personalized therapy in cancer
• Challenges of cancer classification
• Design of future cancer therapies

3. Drug delivery systems for cancer

• Introduction
• Routes of drug delivery in cancer
• Intravenous delivery systems for cancer therapy
• Intravenous versus oral ascorbate for treatment of cancer
• Subcutaneous injection of anticancer agents
• Oral delivery of anticancer agents
• 5-FU combined with eniluracil
• Cyclin D-dependent CDK4 and CDK6 inhibitors
• High dose administration of calcitriol
• Oral fluoropyrimidines
• Oral gefitinib vs intravenous docetaxel
• Oral paclitaxel
• Oral satraplatin
• Oral UFT
• Oral PXD101
• Transdermal drug delivery
• Delivery of the photosensitizer drug δ-amino levulinic acid
• Nanoemulsion-based delivery of caffeine for skin cancer
• Transdermal delivery of methotrexate
• Transdermal nitroglycerine for prostate cancer
• 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
• Improving delivery of protein-polymer anticancer drugs
• Aldoxorubicin
• Linker activated anticancer drug delivery
• Macromolecules as delivery systems for taxanes
• Polyamine conjugates as anticancer agents
• Bacterial vectors 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 biSphere by ultrasound
• Release of drugs from micelles by ultrasound
• Release of drugs from microcapsules by laser
• Chemoembolization
• Anticancer drugs bound to carbon particles
• Anticancer drugs bound to protein microspheres
• Nanoerythrosomes
• Nanobiotechnology-based drug delivery for cancer
• Nanoparticle formulations for drug delivery in cancer
• Anticancer drug particles incorporated in liposomes
• Doxorubicin nanocarriers
• Encapsulating drugs in hydrogel nanoparticles
• Exosomes
• Folate-linked nanoparticles
• Lipid based nanocarriers
• Micelles for drug delivery in cancer
• Minicells for targeted delivery of nanoscale anticancer therapeutics
• Nanobombs for cancer
• Nanodiamonds for local delivery of chemotherapy at site of cancer
• Nanoparticle formulation for enhancing anticancer efficacy of cisplatin
• Nanoparticle formulations of paclitaxel
• Nanoparticles containing albumin and antisense oligonucleotides
• Nanotechnology-based non-invasive refilling of drug delivery depots
• Non-aggregating nanoparticles
• Pegylated nanoliposomal formulation
• Perfluorocarbon nanoparticles
• PFTBA@Alb nanoparticles as enhancers of anti–PD-L1 immunotherapy
• Polymer nanoparticles for drug delivery
• Protein nanocages for penetration of airway mucous and tumors
• Protosphere nanoparticle technology
• Nanoparticles-based targeted delivery of therapeutics for cancer
• Antiangiogenic therapy using nanoparticles
• Carbon magnetic nanoparticles for targeted drug delivery in cancer
• Carbon nanotubes for targeted drug delivery to cancer cells
• CRLX101 for targeted anticancer drug delivery
• DNA aptamer-micelle for targeted drug delivery in cancer
• Fullerenes for enhancing tumor targeting by antibodies
• Gold nanoparticles for targeted drug delivery in cancer
• Hepatic artery infusion of LDL-DHA nanoparticles for liver cancer
• Iron oxide magnetic nanoparticle formulation for drug delivery
• Laser irradiation for targeted release of drugs from nanocontainers
• Lipoprotein nanoparticles targeted to cancer-associated receptors
• Magnetic nanoparticles for remote-controlled drug delivery to tumors
• Monitoring of targeted delivery by nanoparticle-peptide conjugates
• Nanobees for targeted delivery of cytolytic peptide melittin
• Nanocell for targeted drug delivery to tumor
• Nanodroplets for site-specific cancer treatment
• Nanogel-based stealth cancer vaccine targeting macrophages
• Nanoparticle-mediated targeted delivery of peptides into tumors
• Nanoparticle-mediated targeting of MAPK signaling pathway
• Nanoparticles for targeted delivery of concurrent chemoradiation
• Nanostructured hyaluronic acid for targeted drug delivery in cancer
• Nanoparticles as antibody-drug conjugates
• Nanoparticle-coated peptides for tumor targeting
• Nanoparticle-mediated delivery of multiple anticancer agents
• Nanovesicle-mediated drug delivery in cancer
• Polymer nanoparticles for targeted drug delivery in cancer
• Polymersomes for targeted anticancer drug delivery
• Quinic acid-nanoparticle conjugates
• Targeted drug delivery with nanoparticle-aptamer bioconjugates
• Targeted nanoparticles delivery of cisplatin to mitochondrial genome
• Time-delayed, dual-drug nanoparticle delivery system for cancer
• 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
• Nanosensors for targeted drug delivery in cancer
• 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 delivery systems for nanoparticle penetration into tumor tissue
• Combination of diagnostics and therapeutics for cancer
• Biomimetic nanoparticles targeted to tumors
• Dendrimer nanoparticles for targeting and imaging tumors
• Gold nanoparticle plus bombesin for imaging and therapy of cancer
• Gold nanorods for diagnosis plus photothermal therapy of cancer
• Magnetic nanoparticles for imaging as well as therapy of cancer
• Nanobialys for combining MRI with delivery of anticancer agents
• Nanorobotics for detection and targeted therapy of cancer
• pHLIP nanotechnology for detection and targeted therapy of cancer
• Polymer nanobubbles for targeted and controlled drug delivery
• Radiolabeled carbon nanotubes for tumor imaging and targeting
• Targeted therapy with magnetic nanomaterials guided by antibodies
• Ultrasonic tumor imaging and targeted chemotherapy by nanobubbles
• Future of nanobiotechnology and targeted cancer therapy
• Polyethylene glycol technology
• Enzon's PEG technology
• Debiopharm's PEG biconjugate drug delivery platform
• Nektar PEGylation
• PEG Intron
• Single-chain antibody-binding protein technology
• Vesicular systems for drug delivery in cancer
• 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
• Liposome-nucleic acid complexes for anticancer drug delivery
• Non-pegilated liposomal doxorubicin
• Tumor-selective targeted drug delivery via folate-PEG liposomes
• Ultrasound-mediated anticancer drug release from liposomes
• Companies developing liposome-based anticancer drugs
• Pharmacosomes for controlled anticancer drug delivery
• Emulsion formulations of anticancer drugs
• Albumin-based drug carriers
• Anticancer drugs that bind to tumors
• Monoclonal T cell receptor technology
• Radioactive materials for diagnosis and targeted radiotherapy
• Intraperitoneal vs intravenous radioimmunotherapy
• Peptide receptor radionuclide therapy
• Pretargeted radioimmunotherapy of cancer
• Radiolabeled somatostatin receptor antagonists
• Theophylline enhances radioiodide uptake by cancer
• 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
• Iotophoresis for localized delivery of cancer chemotherapy
• Strategies for increasing drug penetration into solid cancers
• Selective destruction of cancer cells
• Hyperbaric oxygen
• Sphingolipids
• Targeting response to transformation-induced oxidative stress
• Targeting enzymes to prevent proliferation of cancer cells
• 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
• Radionuclides delivered with receptor targeting technology
• Targeting ligands specific for cancer cells
• Targeting abnormal DNA in cancer cells
• Targeted delivery by tumor-activated prodrug therapy
• Targeting glutathione S-transferase
• Targeting tumors by exploiting leaky blood vessels
• Targeted drug delivery of anticancer agents with controlled activation
• Targeted delivery of anticancer agents with ReCODE™ technology
• Transmembrane Carrier Systems
• Transferrin-oligomers as targeting carriers in anticancer drug delivery
• Tumor targeting with peptides
• Tumor-targeted delivery of immune checkpoint inhibitors
• Ultrasound and microbubbles for targeted anticancer drug delivery
• Ultrasound for targeted delivery of chemotherapeutics
• Vitamin B12 and folate for targeting cancer chemotherapy
• Cell-based drug delivery in cancer
• Red blood cells as vehicles for drug delivery
• Cells as vehicles for gene delivery
• Drug delivery in relation to circadian rhythms
• Implants for systemic delivery of anticancer drugs
• Drug-eluting polymer implants
• 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
• Vadimezan
• Cadherin inhibitors
• Fosbretabulin tromethamine
• 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-cytokine complexes as vascular targeting agents
• Peptide-polymer conjugates with radionuclides
• Transduction of proteins in vivo
• Tumor targeting by stable toxin (ST) peptides
• Image-guided personalized drug delivery in cancer
• A computational approach to integration of drug delivery methods for cancer

4. Delivery of Biological Therapies for Cancer

• Introduction
• Antisense therapy
• Basics of antisense approaches
• Antisense cancer therapy
• Mechanisms of anticancer effect of antisense oligonucleotides
• Selected antisense drugs in development for cancer
• Antisense targeted to ribonucleotide reductase
• Immune modulatory oligonucleotide
• Ribozyme therapy
• Spiegelmers
• Antisense drug delivery issues
• Strategies to overcome delivery problems of antisense oligonucleotides
• Antisense delivery in microspheres
• Delivery of antisense using nanoparticles
• Delivery across the blood-brain barrier
• Delivery of ribozymes
• Iontophoretic delivery of oligonucleotides
• Liposomes-mediated oligonucleotide delivery
• Neugene antisense drugs
• Oral delivery of oligonucleotides
• Peptide nucleic acid delivery
• Receptor-mediated endocytosis
• Delivery of ribozymes
• Combination of antisense and electrochemotherapy
• Aptamers for combined diagnosis and therapeutics of cancer
• Antisense compounds in clinical trials
• RNA interference
• Basics of RNAi
• Comparison of antisense and RNAi
• RNAi applications in oncology
• siRNA-based cancer immunotherapy
• Delivery of siRNA in cancer
• Delivery of siRNA by nanoparticles
• Delivery of siRNA by nanosize liposomes
• Lipid nanoparticles for delivery of anticancer siRNAs
• Polymer nanoparticles for targeted delivery of anticancer siRNA
• Lipophilic siRNA for targeted delivery to solid tumors
• 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
• Nonviral 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
• Monoclonal antibody gene transfer
• Transfer and expression of intracellular adhesion-1 molecules
• Other gene therapy techniques for immunotherapy of cancer
• Chemokines
• Engineered viruses as anticancer immunotherapy vectors
• Fas (Apo-1)
• IGF (Insulin-Like Growth Factor)
• Major Histocompatibility Complex (MHC) Class I
• Inhibition of immunosuppressive function
• microRNA gene therapy
• 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
• Cancer terminator virus
• Cytokine-induced killer cells for delivery of an oncolytic virus
• Facilitating oncolysis by targeting innate antiviral response by HDIs
• Oncolytic HSV
• Oncolytic adenoviruses
• Oncolytic Coxsackie virus A21
• Oncolytic vesicular stomatitis virus
• Oncolytic measles virus
• Oncolytic paramyxovirus
• Oncolytic reovirus
• Oncolytic vaccinia virus
• Synthetic oncolytic virus
• Monitoring of viral-mediated oncolysis by PET
• Companies developing oncolytic viruses
• Antiangiogenic therapy for cancer
• Apoptotic approach to improve cancer gene therapy
• Bacteria as novel anticancer gene vectors
• Concluding remarks on cancer gene therapy
• Cancer gene therapy companies
• Cell therapy for cancer
• Cellular immunotherapy for cancer
• Treatments for cancer by ex vivo mobilization of immune cells
• Granulocytes as anticancer agents
• Neutrophil granulocytes in antibody-based immunotherapy of cancer
• Use of hematopoietic stem cells for targeted cancer therapy
• Cancer vaccines
• Cell-based cancer vaccines
• Autologous tumor cell vaccines
• Vaccines that simultaneously target different cancer antigens
• Delivery systems for cell-based cancer vaccines
• Intra-lymph node injections of cancer vaccine antigens
• Nucleic acid-based cancer vaccines
• Antiangiogenic DNA cancer vaccine
• DNA cancer vaccines
• Methods of delivery of DNA vaccines
• RNA vaccines
• Viral vector-based cancer vaccines
• Companies involved in nucleic acid-based vaccines
• Genetically modified cancer cells vaccines
• GVAX cancer vaccines
• Genetically modified dendritic cells
• Multipeptide-based cancer vaccines

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
• Methods for evaluation of anticancer drug penetration into brain tumor
• Innovative methods of drug delivery for glioblastoma
• Delivery of anticancer drugs across the blood-brain barrier
• Anticancer agents with increased penetration of BBB
• BBB disruption
• Nanoparticle-based targeted delivery of chemotherapy across the BBB
• Tyrosine kinase inhibitor increases topotecan penetration into CNS
• Bypassing the BBB by alternative methods of drug delivery
• Intranasal perillyl alcohol
• Intraarterial chemotherapy
• Enhancing tumor permeability to chemotherapy
• 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
• CED for receptor-directed cytotoxin therapy
• CED of topotecan
• CED of a modified diphtheria toxin conjugated to transferrin
• CED of nanoliposomal CPT-11
• CED for delivery 131I-chTNT-1/B MAb
• Anticancer drug formulations for targeted delivery to brain tumors
• Intravenous delivery of anticancer agents bearing transferrin
• Liposomes for drug delivery to brain tumors
• MAbs targeted to brain tumors
• Multiple targeted drugs for brain tumors
• Nanoparticles for targeted drug delivery in glioblastoma
• Aurora kinase B siRNA & lactoferrin nanoparticles with temozolomide
• Targeted antiangiogenic/apoptotic/cytotoxic therapies
• Targeted drug delivery to gliomas using cholera toxin subunit B
• Introduction of the chemotherapeutic agent into the CSF pathways
• Intraventricular chemotherapy for meningeal cancer
• Intrathecal chemotherapy
• Interstitial delivery of dexamethasone for reduction of peritumor edema
• Combination of chemotherapy with radiotherapy
• 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
• Chimeric antigen receptor T cells
• Mesenchymal stem cells to deliver treatment for gliomas
• Stem cell-based therapy targeting EGFR in glioblastoma
• Gene therapy for glioblastoma
• Antiangiogenic gene therapy
• Anticancer drug delivery by genetically engineered MSCs
• Gene transfer to brain tumor across the BBB by nanobiotechnology
• Intracerebroventricular delivery of gene therapy for gliomas by NSCs
• Intravenous gene delivery with nanoparticles into brain tumors
• Ligand-directed delivery of dsRNA molecules targeted to EGFR
• MSC-based gene delivery to glioblastoma
• Neural stem cells for drug/gene delivery to brain tumors
• Peptides targeted to glial tumor cells
• RNAi gene therapy of brain cancer
• Single-chain antibody-targeted adenoviral vectors
• Targeting normal brain cells with an AAV vector encoding interferon-
• Treatment of medulloblastoma by suppressing genes in Shh pathway
• Virus-mediated oncolytic therapy of glioblastoma
• Clinical trials of viral oncolysis of glioblastoma
• Oncolytic viral delivery by stem cells for brain metastases
• Future of viral-mediated oncolysis
• Vaccination for glioblastoma
• Cell-based vaccines for glioblastoma
• Peptide vaccines for glioblastoma
• Poliovirus-based vaccine for glioblastoma
• Breast Cancer
• Therapies for breast cancer involving innovative methods of drug delivery
• Injectable biodegradable polymer delivery system for local chemotherapy
• MammoSite brachytherapy
• Monoclonal antibodies targeted to HER2 receptor
• Breast cancer vaccines
• HER-2 DNA AutoVac vaccine
• Recombinant adenoviral ErbB-2/neu vaccine
• Gene vaccine for breast cancer
• NeuVax
• Gene therapy for breast cancer
• Antisense therapy for breast cancer
• Inhibitors of growth factors FGF2 and VEGF for breast cancer
• Targeted multi-drug delivery approach to breast cancer
• Cancer of the cervix and the uterus
• Gene therapy for cervical cancer
• Delivery of chemoradiation therapy
• Cervical cancer vaccines
• Cancer of the liver
• Hepatocellular carcinoma
• Treatment of liver metastases
• Gastrointestinal cancer
• Colorectal cancer
• Oxaliplatin long-circuting liposomes
• Perifosine
• Targeted delivery of triple anticancer therapy by local patch
• Gastrointestinal stromal tumor
• Vaccines for gastrointestinal cancer
• Hematological malignancies
• Leukemia
• Clofarabine
• Ibrutinib
• Idelalisib for CLL
• Multiple myeloma
• Monoclonal antibody therapy in multiple myeloma
• Non-Hodgkin's lymphoma
• Idelalisib for NHL
• Pixantrone
• Rituximab after autologous stem-cell transplantation
• Malignant melanoma
• Targeted therapies for melanoma
• Immunotherapy for malignant melanoma
• Gene therapy for malignant melanoma
• Nasopharangeal carcinoma
• Synergistic effect of gene therapy with 5-FU
• Neuroblastoma
• Genetically modified NSCs for treatment of neuroblastoma
• Non-small cell lung cancer
• Aerosol delivery of anticancer agents for lung cancer
• Aerosol gene delivery for lung cancer
• Complex nanoscale pulmonary delivery of drugs for resistant lung cancer
• Intratumoral administration of anticancer drugs through a bronchoscope
• Ovarian cancer
• Dendritic cell vaccination for ovarian cancer
• Gene Therapy for ovarian cancer
• Innovative drug delivery for ovarian cancer
• Intravenous ascorbate for ovarian cancer
• Intraperitoneal delivery
• Intraperitoneal hyperthermic chemotherapy in ovarian cancer
• Modulation of protein ubiquitination
• Targeting Notch pathway to overcome resistance to chemotherapy
• Pancreatic cancer
• Delivery of chemotherapy for pancreatic cancer
• Local drug delivery
• Localized drug delivery by iontophoresis
• Nanoparticle-based delivery of tumor-penetrating peptides
• Targeted chemotherapy for pancreatic cancer
• Transport properties of pancreatic cancer and gemcitabine delivery
• Vaccine for pancreatic cancer
• Gene therapy for pancreatic cancer
• Correction of altered genes
• Targeted gene therapy
• Targeting in pancreatic adenocarcinoma with cell surface antigens
• Targeted Expression of BikDD gene
• Viral oncolysis in pancreatic cancer
• Prostate cancer
• Alpha emitter radium-223 for targeting bone metastases in cancer
• Brachytherapy for cancer of prostate
• Brachytherapy via paravertebral approach lymph node metastases
• Capridine-beta
• LHRH for prostate cancer
• LHRH analogs
• Histrelin implant
• Immunomodulatory drugs
• MAbs for prostate cancer
• PACLIMER Microspheres
• PRX302
• Targeted therapies for prostate cancer
• Delivery of cisplatin to prostate cancer by nanoparticles
• Delivery of siRNAs to prostate cancer with aptamer-siRNA chimeras
• Delivery of siRNA for prostate cancer with metastases
• Gold nanoparticles targeted to laminin receptor in prostate cancer
• PSA-activated protoxin that kills prostate cancer
• Targeted delivery of a nanoparticulate platinum prodrug
• Targeting oncogene MDM2 in prostate cancer
• Vascular targeting of prostate cancer
• Gene therapy for cancer of prostate
• Experimental studies
• Nanoparticule-based gene therapy for prostate cancer
• Tumor suppressor gene therapy in prostate cancer
• Vaccines for prostate cancer
• Clinical trials of gene therapy for prostate cancer
• Viral oncolysis for prostate cancer
• Combined approaches
• Combined autovaccination and hyperthermia
• Thyroid cancer

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 2019-2029
• Cancer drug market
• Market for leukemia
• Market for lymphoma
• Markets for brain tumors
• Market for breast cancer
• Market for ovarian cancer
• Geographical distribution of cancer markets
• Factors affecting future cancer markets
• Market share according to cancer drug delivery technologies
• Antiangiogenesis therapies
• Antibody drug conjugates
• Antineoplastic drug implants for systemic administration
• Antisense therapy and RNAi
• Cancer vaccines
• Cell/gene therapy
• Liposomes for anticancer drugs
• Monoclonal antibodies
• Modulators of protein ubiquitination
• Strategic aspects of cancer drug delivery
• Unmet needs in cancer drug delivery
• Future of cancer drug delivery
• Cancer drug delivery and pharmacogenomics
• Cancer immunotherapy markets
• 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 2017
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: Selected antiangiogenic agents in development for cancer
Table 2-4: Approaches to cancer therapy based on bacteria
Table 2-5: Cell therapy technologies used for cancer
Table 2-6: Classification of various therapeutic approaches to cancer immunotherapy
Table 2-7: Non-nucleic acid cancer vaccines without genetic modification
Table 2-8: Monoclonal antibodies for cancer approved by the FDA
Table 2-9: Anticancer agents linked to monoclonal antibodies
Table 2-10: Monoclonal antibodies in clinical trials for cancer
Table 2-11: Antibody drug conjugates in clinical trials for cancer
Table 2-12: Third generation boron delivery agents currently under investigation
Table 2-13: Cellular pathways as targets for anticancer therapies
Table 2-14: Examples of anticancer agents that target mitochondrial membranes
Table 2-15: Drugs targeting oncogenes
Table 2-16: PARP inhibitors for cancer therapy
Table 2-17: Cancer therapies based on the P53
Table 2-18: Promise of personalized therapy in cancer
Table 2-19: 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: Approved oral chemotherapy drugs
Table 3-4: Microparticles as therapeutic delivery systems in cancer
Table 3-5: Classification of nanobiotechnology approaches to drug delivery in cancer
Table 3-6: Approved anticancer drugs using nanocarriers
Table 3-7: Clinical trials of anticancer drugs using nanocarriers
Table 3-8: Marketed preparations for liposome-based anticancer drugs
Table 3-9: Clinical trials of liposome-based anticancer drugs
Table 3-10: Strategies for drug delivery in cancer
Table 3-11: Implant systems for delivery of anticancer drugs into tumors
Table 3-12: Targeted delivery of anticancer therapeutics
Table 3-13: Methods of delivery of antiangiogenesis therapies
Table 3-14: 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: Antisense oligonucleotides in clinical trials for cancer
Table 4-4: Companies developing antisense and RNAi therapies for cancer
Table 4-5: Strategies for cancer gene therapy
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 4-10: Cell therapy technologies used for cancer
Table 4-11: Companies developing nucleic acids/genetically modified cells-based cancer vaccines
Table 5-1: Innovative methods of drug delivery for glioblastoma
Table 5-2: Strategies for gene therapy of malignant brain tumors
Table 5-3: Clinical trials of virotherapies for glioblastoma
Table 5-4: Therapies for breast cancer involving innovative methods of drug delivery
Table 5-5: Drug delivery for hepatocellular carcinoma
Table 5-6: Gene therapy for malignant melanoma
Table 5-7: Targeted treatment of non-small cell lung cancer
Table 5-8: Clinical trials of gene therapy in ovarian cancer
Table 5-9: Methods of drug delivery in pancreatic cancer
Table 5-10: Pharmacological strategies under investigation for cancer of the prostate
Table 5-11: Clinical trials of gene therapy for prostate cancer
Table 6-1: Worldwide drug delivery market growth 2020 to 2030
Table 6-2: Worldwide prevalence of cancer according to type of cancer 2020-2030
Table 6-3: Estimated number of cancer patients in major markets 2020-2030
Table 6-4: Worldwide anticancer drug sales for from 2020 to 2030
Table 6-5: Geographical distribution of cancer markets 2020-2030
Table 6-6: Market values of cancer drug delivery technologies from 2020-2030

Figures

Figure 1-1: Structure of PD-1 pathway
Figure 1-2: Signaling pathway changes during adaptation of cancer cell to hypoxia
Figure 1-3: Nitric oxide: tumor enhancement or inhibition
Figure 1-4: Role of nitric oxide in angiogenesis
Figure 1-5: An overview of some key steps in tumor angiogenesis.
Figure 2-1: Targeting tumors with light-emitting engineered bacteria
Figure 2-2: Enhancing tumor-cell visibility to the immune system by viral mimicry
Figure 2-3: Schematic role of T helper cells in immune response to cancer
Figure 2-4: G-MAB™ technology
Figure 2-5: Antimetabolic anticancer effect of SR9243 by inhibiting Warburg effect
Figure 3-1: Cyclacel's Penetratin Transport System for delivery of drugs to targets
Figure 3-2: Linker Activated Drug Release
Figure 3-3: Micelle for drug delivery in cancer
Figure 3-4: Targeted drug delivery with QA-NPs via peritumoral blood vessels
Figure 3-5: Mechanism of action of Targaceutical drugs
Figure 3-6: VIADUR leuprolide acetate using DUROS implant technology
Figure 4-1: Mechanism of action of oncolytic viruses
Figure 5-1: A concept of targeted drug delivery to GBM across the BBB
Figure 5-2:Mechanism of antitumor effects of poliovirus-based vaccine for glioblastoma
Figure 6-1: Unmet needs in cancer drug delivery

Part II: Companies

8. Companies involved in cancer drug delivery

• Introduction
• Profiles of companies
• Collaborations

Tables

Table 8-1: Oncology pipeline of GlaxoSmithKline
Table 8-2: Roche pipeline of oncology products
Table 8-3: Collaborations of companies in cancer drug delivery

Samples