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Drug Repurposing in Cancer Therapy: Approaches and Applications provides comprehensive and updated information from experts in basic science research and clinical practice on how existing drugs can be repurposed for cancer treatment. The book summarizes successful stories that may assist researchers in the field to better design their studies for new repurposing projects. Sections discuss specific topics such as in silico prediction and high throughput screening of repurposed drugs, drug repurposing for overcoming chemoresistance and eradicating cancer stem cells, and clinical investigation on combination of repurposed drug and anticancer therapy. Cancer researchers, oncologists, pharmacologists and several members of biomedical field who are interested in learning more about the use of existing drugs for different purposes in cancer therapy will find this to be a valuable resource. - Presents a systematic and up-to-date collection of the research underpinning the various drug repurposing approaches for a quick, but in-depth understanding on current trends in drug repurposing research - Brings better understanding of the drug repurposing process in a holistic way, combining both basic and clinical sciences - Encompasses a collection of successful stories of drug repurposing for cancer therapy in different cancer types
Drug repurposing or drug repositioning is a new approach to presenting new indications for common commercial and clinically approved existing drugs. For example, chloroquine, an old antimalarial drug, showed promising results for treating COVID-19, interfering with MDR in several types of cancer, and chemosensitizing human leukemic cells.This book focuses on the hypothesis, risk/benefits, and economic impacts of drug repurposing on drug discovery in dermatology, infectious diseases, neurological disorders, cancer, and orphan diseases. It brings together up-to-date research to provide readers with an informative, illustrative, and easy-to-read book useful for students, clinicians, and the pharmaceutical industry.
This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
Cancer cell biology research in general, and anti-cancer drug development specifically, still relies on standard cell culture techniques that place the cells in an unnatural environment. As a consequence, growing tumor cells in plastic dishes places a selective pressure that substantially alters their original molecular and phenotypic properties.The emerging field of regenerative medicine has developed bioengineered tissue platforms that can better mimic the structure and cellular heterogeneity of in vivo tissue, and are suitable for tumor bioengineering research. Microengineering technologies have resulted in advanced methods for creating and culturing 3-D human tissue. By encapsulating the respective cell type or combining several cell types to form tissues, these model organs can be viable for longer periods of time and are cultured to develop functional properties similar to native tissues. This approach recapitulates the dynamic role of cell–cell, cell–ECM, and mechanical interactions inside the tumor. Further incorporation of cells representative of the tumor stroma, such as endothelial cells (EC) and tumor fibroblasts, can mimic the in vivo tumor microenvironment. Collectively, bioengineered tumors create an important resource for the in vitro study of tumor growth in 3D including tumor biomechanics and the effects of anti-cancer drugs on 3D tumor tissue. These technologies have the potential to overcome current limitations to genetic and histological tumor classification and development of personalized therapies.
Drug development can be time-consuming and expensive. Recent estimates suggest that, on average, it takes 10 years and at least $1 billion to bring a drug to market. Given the time and expense of developing drugs de novo, pharmaceutical companies have become increasingly interested in finding new uses for existing drugs - a process referred to as drug repurposing or repositioning. Historically, drug repurposing has been largely an unintentional, serendipitous process that took place when a drug was found to have an offtarget effect or a previously unrecognized on-target effect that could be used for identifying a new indication. Perhaps the most recognizable example of such a successful repositioning effort is sildenafil. Originally developed as an anti-hypertensive, sildenafil, marketed as Viagra and under other trade names, has been repurposed for the treatment of erectile dysfunction and pulmonary arterial hypertension. Viagra generated more than $2 billion worldwide in 2012 and has recently been studied for the treatment of heart failure. Given the widespread interest in drug repurposing, the Roundtable on Translating Genomic-Based Research for Health of the Institute of Medicine hosted a workshop on June 24, 2013, in Washington, DC, to assess the current landscape of drug repurposing activities in industry, academia, and government. Stakeholders, including government officials, pharmaceutical company representatives, academic researchers, regulators, funders, and patients, were invited to present their perspectives and to participate in workshop discussions. Drug Repurposing and Repositioning is the summary of that workshop. This report examines enabling tools and technology for drug repurposing; evaluates the business models and economic incentives for pursuing a repurposing approach; and discusses how genomic and genetic research could be positioned to better enable a drug repurposing paradigm.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
Volume 19, entitled Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic of the series Metal Ions in Life Sciences centers on the role of metal ions in clinical medicine. Metal ions are tightly regulated in human health: while essential to life, they can be toxic as well. Following an introductory chapter briefly discussing several important metal-related drugs and diseases and a chapter about drug development, the focus is fi rst on iron: its essentiality for pathogens and humans as well as its toxicity. Chelation therapy is addressed in the context of thalassemia, its relationship to neurodegenerative diseases and also the risks connected with iron administration are pointed out. A subject of intense debate is the essentiality of chromium and vanadium. For example, chromium(III) compounds are taken as a nutritional supplement by athletes and bodybuilders; in contrast, chromate, Cr(VI), is toxic and a carcinogen for humans. The benefi cial and toxic effects of manganese, cobalt, and copper on humans are discussed. The need for antiparasitic agents is emphasized as well as the clinical aspects of metal-containing antidotes for cyanide poisoning. In addition to the essential and possibly essential ones, also other metal ions play important roles in human health, causing harm (like the metalloid arsenic, lead or cadmium) or being used in diagnosis or treatment of human diseases, like gadolinium, gallium, lithium, gold, silver or platinum. The impact of this vibrant research area on metals in the clinic is provided in 14 stimulating chapters, written by internationally recognized experts from the Americas, Europe and China, and is manifested by approximately 2000 references, and about 90 illustrations and tables. Essential Metals in Medicine: Therapeutic Use and Toxicity of Metal Ions in the Clinic is an essential resource for scientists working in the wide range from pharmacology, enzymology, material sciences, analytical, organic, and inorganic biochemistry all the way through to medicine ... not forgetting that it also provides excellent information for teaching.
Rare diseases collectively affect millions of Americans of all ages, but developing drugs and medical devices to prevent, diagnose, and treat these conditions is challenging. The Institute of Medicine (IOM) recommends implementing an integrated national strategy to promote rare diseases research and product development.
An essential outline of the main facets of polypharmacology in drug discovery research Extending drug discovery opportunities beyond the "one drug, one target" philosophy, a polypharmacological approach to the treatment of complex diseases is emerging as a hot topic in both industry and academic research. Polypharmacology in Drug Discovery presents an overview of the various facets of polypharmacology and how it can be applied as an innovative concept for developing medicines for treating bacterial infections, epilepsy, cancer, psychiatric disorders, and more. Filled with a collection of instructive case studies that reinforce the material and illuminate the subject, this practical guide: Covers the two-sided nature of polypharmacology—its contribution to adverse drug reactions and its benefit in certain therapeutic drug classes Addresses the important topic of polypharmacology in drug discovery, a subject that has not been thoroughly covered outside of scattered journal articles Overviews state-of-the-art approaches and developments to help readers understand concepts and issues related to polypharmacology Fosters interdisciplinary drug discovery research by embracing computational, synthetic, in vitro and in vivo pharmacological and clinical aspects of polypharmacology A clear road map for helping readers successfully navigate around the problems involved with promiscuous ligands and targets, Polypharmacology in Drug Discovery provides real examples, in-depth explanations and discussions, and detailed reviews and opinions to spark inspiration for new drug discovery projects.
This book is the third volume on this subject and focuses on the recent advances of nanopharmaceuticals in cancer, dental, dermal and drug delivery applications and presents their safety, toxicity and therapeutic efficacy. The book also includes the transport phenomenon of nanomaterials and important pathways for drug delivery applications. It goes on to explain the toxicity of nanoparticles to different physiological systems and methods used to assess this for different organ systems using examples of in vivo systems.