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Drug Delivery in Cancer - technologies, markets and companies Published on September 2011
Report Summary Drug delivery remains a challenge in management of cancer. Approximately 12.5 million new cases of cancer are being diagnosed worldwide each year and considerable research is in progress for drug discovery for cancer. Cancer drug delivery is no longer simply wrapping up cancer drugs in a new formulations for different routes of delivery. The focus is on targeted cancer therapy. The newer approaches to cancer treatment not only supplement the conventional chemotherapy and radiotherapy but also prevent damage to normal tissues and prevent drug resistance. Innovative cancer therapies are based on current concepts of molecular biology of cancer. These include antiangiogenic agents, immunotherapy, bacterial agents, viral oncolysis, targeting of cyclic-dependent kinases and tyrosine kinase receptors, antisense approaches, gene therapy and combination of various methods. Important methods of immunotherapy in cancer involve use of cytokines, monoclonal antibodies, cancer vaccines and immunogene therapy. Several innovative methods of drug delivery are used in cancer. These include use of microparticles as carriers of anticancer agents. These may be injected into the arterial circulation and guided to the tumor by magnetic field for targeted drug delivery. Polyethylene glycol (PEG) technology has been used to overcome some of the barriers to anticancer drug delivery. Encapsulating anticancer drugs in liposomes enables targeted drug delivery to tumor tissues and prevents damage to the normal surrounding tissues. Monoclonal antibodies can be used for the delivery of anticancer payloads such as radionucleotides, toxins and chemotherapeutic agents to the tumors. Antisense oligonucleotides have been in clinical trials for cancer for some time now. RNAi has also been applied in oncology. Small interfering RNAs (siRNAs) can be targeted to tumors and one example is suppression of H-ras gene expression indicating the potential for application in therapy of ovarian cancer. Cancer gene therapy is a sophisticated form of drug delivery for cancer. Various technologies and companies developing them are described. Nucleic acid-based cancer vaccines are also described. Drug delivery strategies vary according to the type and location of cancer. Role of drug delivery in the management of cancers of the brain, the bladder, the breast, the ovaries and the prostate are used as examples to illustrate different approaches both experimental and clinical. Biodegradable implants of carmustine are already used in the treatment of malignant brain tumors. The market value of drug delivery technologies and the anticancer drugs are difficult to separate. Cancer market estimates from 2010-2020 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 212 companies involved in developing innovative cancer therapies and methods of delivery are presented along with their 240 collaborations. The bibliography contains over 600 publications that are cited in the report.The report is supplemented with 58 tables and 8 figures.
Table of Content TABLE OF CONTENTS
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>> Get this Report Now by email! 0. Executive Summary 17 1. Introduction to cancer therapy 19 Molecular biology of cancer 19 The genesis of cancer 19 Normal cell cycle and growth 19 Oncogenes 20 Tumor Suppressor Genes 20 Role of microRNAs in cancer 22 Role of Bub 1 gene in cell division 22 Mechanism of DNA damage in Fanconi anemia leading to leukemia 23 Accumulation of random mutations 23 Chromosomal instability 23 Aneuploidy 24 Telomeres and cancer 24 DNA methylation and cancer 25 Anticancer treatments based on RNA regulation of genes 25 Hallmarks of cancer 26 Self-sufficiency of tumor proliferation 26 Apoptosis 27 Therapeutic implications of apoptosis in cancer 27 Autophagy 29 Tumor angiogenesis 29 Acquisition of a potential for unlimited replication 31 Invasion and metastases 31 Tumor suppressor genes and metastases 32 Cancer biomarkers 32 Molecular imaging of cancer 32 Cancer genomics 33 Gene expression profiling in cancer 33 Cancer proteomics 33 Limitations of genomics and proteomics for understanding cancer 34 Cancer microenvironment 34 Epidemiology of cancer 35 Current management of cancer 35 Chemotherapy 36 Limitations of cancer chemotherapy 36 Radiotherapy 36 Brachytherapy 37 Surgery 37 Basics of drug delivery in cancer 37 Historical landmarks in cancer drug delivery 37 2. Innovative treatments for cancer 39 Introduction 39 Selective estrogen receptor modulators 40 Antiangiogenic strategies for cancer 41 Development of antiangiogenic therapies 41 Classification of antiangiogenic agents 41 Examples of antiangiogenic agents 43
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>> Get this Report Now by email! Basics of RNAi 232 Comparison of antisense and RNAi 232 RNAi applications in oncology 233 siRNA-based cancer immunotherapy 234 Delivery of siRNA in cancer 234 Delivery of siRNA by nanoparticles 235 Delivery of siRNA by nanosize liposomes 235 Lipid nanoparticles for delivery of anticancer siRNAs 236 Polymer nanoparticles for targeted delivery of anticancer siRNA 236 Companies developing cancer therapies based on antisense and RNAi 237 DNA interference 238 Cancer gene therapy 238 Basics of gene therapy 238 Strategies for cancer gene therapy 239 Gene transfer techniques as applied to cancer gene therapy 240 Viral vectors 240 Nonviral vectors 241 A polymer approach to gene therapy for cancer 241 Direct gene delivery to the tumor 242 Injection into tumor 242 Reversible electroporation 243 Hematopoietic gene transfer 244 Genetic modification of human hematopoietic stem cells 244 Gene-based strategies for immunotherapy of cancer (immunogene therapy) 245 Cytokine gene therapy 245 Monoclonal antibody gene transfer 249 Transfer and expression of intracellular adhesion-1 molecules 249 Other gene-based techniques of immunotherapy of cancer 249 Fas (Apo-1) 249 Chemokines 249 Major Histocompatibility Complex (MHC) Class I 250 IGF (Insulin-Like Growth Factor) 250 Inhibition of immunosuppressive function 250 microRNA gene therapy 251 Delivery of toxic genes to tumor cells for eradication (molecular chemotherapy) 251 Gene-directed enzyme prodrug therapy 251 Combination of gene therapy with radiotherapy 252 Multipronged therapy of cancer with microencapsulated cells 253 Correction of genetic defects in cancer cells (mutation compensation) 253 Targeted gene therapy for cancer 254 Transcriptional targeting for cancer gene therapy 254 Targeted epidermal growth factor-mediated DNA delivery 254 Gene-based targeted drug delivery to tumors 254 Targeting gene expression to hypoxic tumor cells 255 Targeting gene expression by progression-elevated gene-3 promoter 255 Targeted delivery of retroviral particles hitchhiking on T cells 256 Targeting tumors with genetically modified T cells 256 Targeting tumors by genetically engineered stem cells 256
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