Personalized Immuno-Oncology.

Cancer immunotherapy, which aims to control the immune system to eradicate cancer cells and prevent their spread, needs to be personalized because anticancer immune responses can be inhibited in several ways that vary from patient to patient. Cancer immunotherapy includes pharmaceuticals such as immune checkpoint inhibitors and monoclonal antibodies (MAbs) as well as cell therapy, immunogene therapy, and vaccines. Combination of programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) drugs with other immunotherapy drugs, for example, antibody-drug conjugates, as well as combination of PD-1/PD-L1 drugs with other therapies, for example, chemotherapy and radiation therapy, are being explored. Biomarkers are important for predicting the response to immunotherapy. Molecular diagnostics and sequencing are important technologies for guiding treatment in immuno-oncology. Genomic profiling of tumor mutational burden may enhance the predictive utility of PD-L1 expression and facilitate personalized combination immunotherapy. Optimization of personalized immuno-oncology requires integration of several technologies and selection of those best suited for an individual patient. Advances in immuno-oncology are also attributed to technologies for targeted delivery of anticancer therapeutics such as antigen-capturing nanoparticles for precision targeting and selective delivery. A breakthrough in cell therapy of cancer is a chimeric antigen receptors-T cell, which combines the antigen-binding site of a MAb with the signal activating machinery of a T cell, freeing antigen recognition from major histocompatibility complex restriction. Gene-editing tools such as clustered regularly interspaced short palindromic repeats have a promising application for removing alloreactivity and decreasing immunogenicity of third-party T cells. In conclusion, personalized immuno-oncology is one of the most promising approaches to management of cancer.

An Overview of Drug Delivery Systems.

This is an overview of the current drug delivery systems (DDSs) starting with various routes of drug administration. Various drug formulations are then described as well as devices used for drug delivery and targeted drug delivery. There has been a considerable increase in the number of new biotechnology-based therapeutics. Most of these are proteins and peptides, and their delivery present special challenges. Cell and gene therapies are sophisticated methods of delivery of therapeutics. Nanoparticles are important for refining drug delivery. In addition to being vehicles for drug delivery, nanoparticles can be used as pharmaceuticals as well as diagnostics. Most of the advances in targeted drug delivery have occurred in therapy of cancer. Drug delivery to the brain across the blood-brain barrier presents many challenges. Refinements in drug delivery will facilitate the development of personalized medicine. The ideal DDS is defined. Commercial aspects, challenges, and future of DDSs are discussed.

Role of Nanobiotechnology in Drug Delivery.

This chapter is a brief overview of use of nanobiotechnology in drug delivery. Several types of nanoparticles are available. Nanoparticulate formulations of normally used drugs have increased efficacy due to improved absorption and require lower dosage with less side effects than standard formulations. Nanobiotechnology also facilitates targeted drug delivery of anticancer drugs, which is important for the management of cancer. Nanoparticles also facilitate crossing of biological barriers in the human body for drug delivery to targeted organs, for example, crossing the blood-brain barrier to reach the brain. Nanobiotechnology applications in delivery of biological therapies are expanding in areas such as cell and gene therapies, siRNAs, and monoclonal antibodies. Some nanoparticles can carry more than one therapeutic molecule enabling multimodal therapy and combination with physical modalities such as radiotherapy in cancer. Nanorobotics is developing with applications in drug delivery, particularly for cancer. Other anticipated developments in this area include use of nanotechnology for creating intelligent drug release devices.

A Critical Overview of Targeted Therapies for Glioblastoma.

Over the past century, treatment of malignant tumors of the brain has remained a challenge. Refinements in neurosurgical techniques, discovery of powerful chemotherapeutic agents, advances in radiotherapy, applications of biotechnology, and improvements in methods of targeted delivery have led to some extension of length of survival of glioblastoma patients. Refinements in surgery are mentioned because most of the patients with glioblastoma undergo surgery and many of the other innovative therapies are combined with surgery. However, cure of glioblastoma has remained elusive because it requires complete destruction of the tumor. Radical surgical ablation is not possible in the brain and even a small residual tumor leads to rapid recurrence that eventually kills the patient. Blood-brain barrier (BBB) comprising brain endothelial cells lining the cerebral microvasculature, limits delivery of drugs to the brain. Even though opening of the BBB in tumor core occurs locally, BBB limits systemic chemotherapy especially at the tumor periphery, where tumor cells invade normal brain structure comprising intact BBB. Comprehensive approaches are necessary to gain maximally from promising targeted therapies. Common methods used for critical evaluation of targeted therapies for glioblastoma include: (1) novel methods for targeted delivery of chemotherapy; (2) strategies for delivery through BBB and blood-tumor barriers; (3) innovations in radiotherapy for selective destruction of tumor; (4) techniques for local destruction of tumor; (5) tumor growth inhibitors; (6) immunotherapy; and (7) cell/gene therapies. Suggestions for improvements in glioblastoma therapy include: (1) controlled targeted delivery of anticancer therapy to glioblastoma through the BBB using nanoparticles and monoclonal antibodies; (2) direct introduction of genetically modified bacteria that selectively destroy cancer cells but spare the normal brain into the remaining tumor after resection; (3) use of better animal models for preclinical testing; and (4) personalized/precision medicine approaches to therapy in clinical trials and translation into practice of neurosurgery and neurooncology. Advances in these techniques suggest optimism for the future management of glioblastoma.

Personalized Management of Cardiovascular Disorders.

Personalized management of cardiovascular disorders (CVD), also referred to as personalized or precision cardiology in accordance with general principles of personalized medicine, is selection of the best treatment for an individual patient. It involves the integration of various "omics" technologies such as genomics and proteomics as well as other new technologies such as nanobiotechnology. Molecular diagnostics and biomarkers are important for linking diagnosis with therapy and monitoring therapy. Because CVD involve perturbations of large complex biological networks, a systems biology approach to CVD risk stratification may be used for improving risk-estimating algorithms, and modeling of personalized benefit of treatment may be helpful for guiding the choice of intervention. Bioinformatics tools are helpful in analyzing and integrating large amounts of data from various sources. Personalized therapy is considered during drug development, including methods of targeted drug delivery and clinical trials. Individualized recommendations consider multiple factors - genetic as well as epigenetic - for patients' risk of heart disease. Examples of personalized treatment are those of chronic myocardial ischemia, heart failure, and hypertension. Similar approaches can be used for the management of atrial fibrillation and hypercholesterolemia, as well as the use of anticoagulants. Personalized management includes pharmacotherapy, surgery, lifestyle modifications, and combinations thereof. Further progress in understanding the pathomechanism of complex cardiovascular diseases and identification of causative factors at the individual patient level will provide opportunities for the development of personalized cardiology. Application of principles of personalized medicine will improve the care of the patients with CVD.

Role of Proteomics in the Development of Personalized Medicine.

Advances in proteomic technologies have made import contribution to the development of personalized medicine by facilitating detection of protein biomarkers, proteomics-based molecular diagnostics, as well as protein biochips and pharmacoproteomics. Application of nanobiotechnology in proteomics, nanoproteomics, has further enhanced applications in personalized medicine. Proteomics-based molecular diagnostics will have an important role in the diagnosis of certain conditions and understanding the pathomechanism of disease. Proteomics will be a good bridge between diagnostics and therapeutics; the integration of these will be important for advancing personalized medicine. Use of proteomic biomarkers and combination of pharmacoproteomics with pharmacogenomics will enable stratification of clinical trials and improve monitoring of patients for development of personalized therapies. Proteomics is an important component of several interacting technologies used for development of personalized medicine, which is depicted graphically. Finally, cancer is a good example of applications of proteomic technologies for personalized management of cancer.

Current status and future prospects of drug delivery systems.

This is an overview of the current drug delivery systems (DDS) starting with various routes of drug administration. Various drug formulations are then described as well as devices used for drug delivery and targeted drug delivery. There has been a considerable increase in the number of new biotechnology-based therapeutics. Most of these are proteins and peptides, and their delivery presents special challenges. Cell and gene therapies are sophisticated methods of delivery of therapeutics. Nanoparticles are considered to be important in refining drug delivery; they can be pharmaceuticals as well as diagnostics. Refinements in drug delivery will facilitate the development of personalized medicine in which targeted drug delivery will play an important role. There is discussion about the ideal DDS, commercial aspects, challenges, and future prospects.

Nanobiotechnology-based strategies for crossing the blood-brain barrier.

The blood-brain barrier (BBB) is meant to protect the brain from noxious agents; however, it also significantly hinders the delivery of therapeutics to the brain. Several strategies have been employed to deliver drugs across this barrier and some of these may do structural damage to the BBB by forcibly opening it to allow the uncontrolled passage of drugs. The ideal method for transporting drugs across the BBB should be controlled and should not damage the barrier. Among the various approaches that are available, nanobiotechnology-based delivery methods provide the best prospects for achieving this ideal. This review describes various nanoparticle (NP)-based methods used for drug delivery to the brain and the known underlying mechanisms. Some strategies require multifunctional NPs combining controlled passage across the BBB with targeted delivery of the therapeutic cargo to the intended site of action in the brain. An important application of nanobiotechnology is to facilitate the delivery of drugs and biological therapeutics for brain tumors across the BBB. Although there are currently some limitations and concerns for the potential neurotoxicity of NPs, the future prospects for NP-based therapeutic delivery to the brain are excellent.

Personalized cancer vaccines.

IMPORTANCE OF THE FIELD: Personalized medicine has extended to management of cancer and implies prescription of specific therapeutics best suited for an individual patient and the type of tumor. These principles have been applied to cancer vaccines. AREAS COVERED IN THIS REVIEW: Various cancer vaccines that can be personalized. Tumor-derived vaccines have been used and active immunotherapy based on antigens specific to the tumor. Dendritic cells (DCs) can prime tumor-specific T cell responses and are considered potentially effective vaccines for cancer. DCs may be genetically modified or fused with tumor cells. Adoptive cell therapy is based on autologous antigen-specific T lymphocytes. Personalized peptide vaccination has been combined with chemotherapy. Clinical trials have been conducted. There have been many failures but a selection of those currently in progress is presented. WHAT THE READER WILL GAIN: An overview of various types of personalized cancer vaccines, their mechanism of action and current status of development. Causes of failure of clinical trials and concepts of an ideal personalized cancer vaccine are presented. TAKE HOME MESSAGE: A number of approaches are available for personalized cancer vaccines with variable degree of success. There are several challenges and needs for refinement of methods but it remains a promising area of cancer therapy.

Innovative diagnostic technologies and their significance for personalized medicine.

Molecular diagnostics plays an important role in the development of personalized medicine. Innovative diagnostic technologies that are increasingly utilized in personalizing treatment include novel polymerase chain reaction (PCR), direct molecular analysis without amplification, DNA sequencing, biochips/microarrays, and nanobiotechnologies. Technologies for detection of copy number variations, single nucleotide polymorphisms, and cytogenetic alterations provide basic information for personalized medicine. Molecular diagnostic technologies are used for the detection of biomarkers, which may form the common basis of diagnostics and therapeutics. Finally, integration of diagnostics with therapeutics is an important component of personalized medicine.

Personalized clinical laboratory diagnostics.

Molecular diagnostics play an important role in development of personalized medicine and may be termed personalized diagnostics. This chapter shows the role of various diagnostic technologies in personalizing treatment. Besides polymerase chain reaction (PCR), several non-PCR methods, biochips/microarrays, and nanobiotechnologies play an important role. Technologies for biomarkers, single nucleotide polymorphisms (SNPs), and cytogenetics provide basic information for personalized medicine. Finally, integration of diagnostics with therapeutics is an important component of personalized medicine. Future challenges and prospects of personalized diagnostics are discussed.

The role of nanobiotechnology in drug discovery.

The potential applications of nanotechnology in life sciences, particularly nanobiotechnology, include those for drug discovery. This chapter shows how several of the nanotechnologies including nanoparticles and various nanodevices such as nanobiosensors and nanobiochips are being used to improve drug discovery. Nanoscale assays using nanoliter volumes contribute to cost saving. Some nanosubstances such as fullerenes are drug candidates. There are some safety concerns about the in vivo use of nanoparticles that are being investigated. However, future prospects for applications in healthcare of drugs discovered through nanotechnology and their role in the development of personalized medicine appear to be excellent.

Current challenges and future prospects in management of neuropathic pain.

Management of neuropathic pain is a challenge, as the currently available drugs usually do not target the multiple underlying mechanisms. This article will briefly review the currently available therapies for neuropathic pain as an introduction to those in clinical trials. The two most common conditions in clinical trials of neuropathic pain are diabetic neuropathy and postherpetic neuralgia. Central neuropathic pain remains a challenge in management. Future prospects of finding suitable drugs for neuropathic pain depend on an improved understanding of pain mechanisms. Biomarkers will facilitate the development of novel pain therapies. Molecular approaches to neuropathic pain include cell and gene therapies as well as RNAi-based treatments. Some of the novel targets for developing therapies for neuropathic pain include chemokine receptors, glial cells and cytokines. The review includes various suggestions for management of neuropathic pain, including multidisciplinary and personalized approaches. Considerable improvements are anticipated in the management of neuropathic pain in the next 5 years, although it is difficult to predict the chances of success of any particular product in development, considering the high rate of failures of previous trials.

Drug delivery systems - an overview.

This is an overview of drug delivery systems (DDS), starting with various routes of drug administration. Various drug formulations, as well as devices used for drug delivery and targeted drug delivery, are then described. Delivery of proteins and peptides presents special challenges. Nanoparticles are considered to be important in refining drug delivery; they can be pharmaceuticals as well as diagnostics. Refinements in drug delivery will facilitate the development of personalized medicine, which includes pharmacogenomics, pharmacogenetics, and pharmacoproteomics. The ideal DDS, commercial aspects, current achievements, challenges, and future prospects are also discussed.

Innovations, challenges and future prospects of oncoproteomics.

Oncoproteomics is playing an increasingly important role in the diagnosis and management of cancer as well as in the development of personalized treatment of cancer. Innovative proteomic technologies relevant to cancer are described briefly, which are helping in the understanding of mechanism of drug resistance in cancer and will provide some leads to improve the management. Most important of these are nanoproteomics, i.e. application of nanobiotechnology to proteomics is playing an important role in nanooncology. Examples of some cancers will be given to point out the challenges and future prospects of oncoproteomics including those involving translation of technologies from the bench to the bedside.

Recent advances in clinical oncoproteomics.

Oncoproteomics is the application of proteomic technologies in cancer. Considerable progress has been made during the past decade in the refinement of proteomic technologies and their application for understanding the disease's pathological mechanisms, discovery of biomarkers and diagnosis. Proteomics has been applied in anticancer drug discovery and for personalized management of cancer. Proteins can be identified from the blood or directly from the tumor tissue by laser capture microdissection (LCM) and tissue microarrays. Protein biochips can be used for diagnosis as well as monitoring in clinical trials. Nanobiotechnology has refined the use of proteomics and nanoproteomics and has improved most current protocols including protein purification/display and automated identification of protein traces in minute samples. Due to some limitations, proteomics alone is not enough to provide a complete picture of cancer. Other "-omics" technologies such as genomics are used in integrated approaches. Proteomic studies through light tumor invasiveness and drug resistance. Examples of applications of oncoproteomics are given for cancers of various organs such as the brain, breast, colon and rectum, prostate, and leukemia. In conclusion, proteomics will play an important role in diagnosing cancer and developing personalized treatment of cancer.

Cancer biomarkers: current issues and future directions.

Cancer biomarkers and characteristics of an ideal biomarker for cancer are discussed in this review, as well as technologies for their detection. The focus of this article is on the use of biomarkers for anticancer drug development and clinical applications, including determination of prognosis as well as monitoring of response to therapy. Types of biomarkers include methylated DNA sequences, mitochondrial DNA and microRNA. Within clinical research, oncology is expected to have the largest gains from biomarkers over the next five to ten years. Development of personalized medicine for cancer is closely linked to biomarkers, which may serve as the basis for diagnosis, drug discovery and monitoring of diseases. A major challenge in development of cancer biomarkers will be the integration of proteomics with genomics and metabolomics data and their functional interpretation in conjunction with clinical data and epidemiology.