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PRINTER FRIENDLY

Drug Delivery in Cancer - Technologies, Markets & Companies

  • ID: 4748166
  • Report
  • 733 Pages
  • Jain PharmaBiotech
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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 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  
Quinic acid-nanoparticle conjugates  
Nanoparticle-mediated delivery of multiple anticancer agents
Polymer nanoparticles for targeted drug delivery in cancer
Polymersomes for targeted anticancer drug delivery  
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
I-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: 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.

Note: Product cover images may vary from those shown
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