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Drug Delivery in Cancer - Technologies, Markets & Companies

  • ID: 4748166
  • Report
  • December 2019
  • 733 Pages
  • Jain PharmaBiotech
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Drug delivery remains a challenge in the 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 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 the 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 2018-2028 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 238 companies involved in developing innovative cancer therapies and methods of delivery are presented along with their 289 collaborations. The bibliography contains over 650 publications that are cited in the report. The report is supplemented with 67 tables and 20 figures.

The report contains information on the following:

  • Innovative treatments for cancer
  • Drug delivery systems for cancer
  • Antisense, RNAi and gene therapy for cancer
  • Delivery strategies according to cancer type and location
  • Cancer drug delivery markets
  • Companies
Note: Product cover images may vary from those shown
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Part I: Technologies & 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
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
Cancer immunotherapy
Cytokines
Epigenetic modulators and cancer immunotherapies
STING activation and antitumor immunity
Cancer vaccines
5T4 as a target for cancer immunotherapy
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
Chemoimmunotherapy  
Concluding remarks about cancer vaccines
Targeted delivery of peptides to tumor-associated macrophages
Targeting cancer stem cells  
Monoclonal antibodies  
Murine MAbs  
Humanized MAbs  
Actions and uses of MAbs in cancer  
Anti PD-1 and anti PD-L1 MAbs
Targeted antibody-based cancer therapy  
Antibody–cytokine fusion proteins  
Antibody ARGX-115 for targeting immunosuppressive effect of Tregs  
Antibody J591 for targeted delivery of anticancer therapy  
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
Antibody-drug conjugates  
Kadcyla  
Adcetris  
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
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  
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  
Micronized droplets of olive oil
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
Vaccination for glioblastoma
Cell-based vaccines for glioblastoma  
Peptide vaccines for glioblastoma
Poliovirus-based vaccine for glioblastoma
Viral oncolysis of brain tumors
Clinical trials of viral oncolysis of glioblastoma
Oncolytic viral delivery by stem cells for brain metastases  
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 2018-2028
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: Non-nucleic acid cancer vaccines without genetic modification  
Table 2-7: Monoclonal antibodies for cancer approved by the FDA  
Table 2-8: Anticancer agents linked to monoclonal antibodies  
Table 2-9: Monoclonal antibodies in clinical trials for cancer  
Table 2-10: Antibody drug conjugates in clinical trials for cancer  
Table 2-11: Third generation boron delivery agents currently under investigation  
Table 2-12: Cellular pathways as targets for anticancer therapies
Table 2-13: Examples of anticancer agents that target mitochondrial membranes
Table 2-14: Drugs targeting oncogenes  
Table 2-15: PARP inhibitors for cancer therapy  
Table 2-16: Cancer therapies based on the P53
Table 2-17: Promise of personalized therapy in cancer  
Table 2-18: 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 oncolytic virotherapy against glioblastoma  
Table 5-4: Clinical trials of virotherapies for glioblastoma  
Table 5-5: Therapies for breast cancer involving innovative methods of drug delivery  
Table 5-6: Drug delivery for hepatocellular carcinoma  
Table 5-7: Gene therapy for malignant melanoma  
Table 5-8: Targeted treatment of non-small cell lung cancer  
Table 5-9: Clinical trials of gene therapy in ovarian cancer
Table 5-10: Methods of drug delivery in pancreatic cancer  
Table 5-11: Pharmacological strategies under investigation for cancer of the prostate  
Table 5-12: Clinical trials of gene therapy for prostate cancer  
Table 6-1: Worldwide drug delivery market growth 2018 to 2028  
Table 6-2: Worldwide prevalence of cancer according to type of cancer 2018-2028
Table 6-3: Estimated number of cancer patients in major markets 2018-2028  
Table 6-4: Worldwide anticancer drug sales for from 2018 to 2028  
Table 6-5: Geographical distribution of cancer markets 2018-2028  
Table 6-6: Market values of cancer drug delivery technologies from 2018-2028

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

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

Note: Product cover images may vary from those shown
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