This Research Topic is part of a series with: Multi-targeted Natural Products as Cancer Therapeutics: Challenges and Opportunities, Volume II Cancer remains a leading cause of disease-related deaths worldwide, despite recent advances in our understanding of cancer initiation, progression, and metastasis. Chemotherapy and radiotherapy have been used as standard non-surgical treatments of human cancer for decades, however, the survival rates of patients with cancer, especially those with advanced diseases are still very low due to the high toxicities of these treatments as well as the severe side effects. This fact has motivated researchers to discover new cancer therapeutics with minimum side effects, which intensively promotes the rapid development of single specific molecule-targeted therapies (SSMTT). Many efforts have been made in world-wide cancer drug discovery research and several single molecule-targeted therapies have been successfully developed. Unfortunately, most of the investments failed because cancer is a genetic disease and always harbors multiple alternations of molecules or genes at the genomic, genetic and epigenetic levels. The inhibition of a single molecule or signaling pathway by SSMTT frequently results in a hyperactive compensation of other cancer-related molecules and signaling pathways as well as the subsequent development of drug resistance. Therefore, identifying multi-targeted therapies, i.e. drugs that are able to target multiple cancer-related genes, proteins, or signaling pathways is a more promising way to success in developing new cancer therapeutics. Natural products, especially those from traditional Chinese medicine and folk remedies in other countries are an extraordinarily important source for new drug discovery over the past decades. Of note, many natural products have often been demonstrated to target several crucial genes or proteins in cancer-related signaling networks and exert synergistic effects. For example, Japonicone A, a dimeric sesquiterpenoid from the medicinal plant Inula japonica, has been found to inhibit tumor growth and metastasis by dually targeting the TNF-α/NF-κB and p53/MDM2 signaling pathways. Traditionally, researchers have believed that the multi-targeting mechanisms of natural products have limited their use in cancer treatment due to the low specificity and potential side effects. The growing interest in developing multi-targeted cancer therapies may provide another golden opportunity to develop natural products as new cancer therapeutics. Nevertheless, critical investigations for a comprehensive understanding of the molecular mechanisms of natural products also mean more challenges. Our long-term goals are to fully understand the molecular targets and mechanisms of action of anticancer natural products and develop them as novel cancer preventive and therapeutic agents. The specific goal of this Research Topic is to bring together the recent findings of newly identified anticancer natural products, especially those with multiple molecular targets. Papers (Original Research articles or Reviews) which discuss the in vitro and in vivo efficacy and pharmacological and toxicological properties of natural products are also welcome to be submitted. Guidelines for the conception and review of submissions As many anticancer drugs working as cytotoxic compounds have non-selective effects annihilating their potential therapeutic benefits, manuscripts are advised to provide evidence of a significant selectivity towards cancer cells (vs. healthy cells). Specifically, if the studied anticancer drug or modality does not target an oncogenic pathway, the authors should make every effort possible to prove that the cytotoxic or cytostatic effects they have identified exhibit selectivity for cancer cells (ideally 1 log difference in EC50 or IC50) vs. non-malignant cells (eg, fibroblasts or primary culture of cells). The authors should also demonstrate the applicability of their anticancer modalities on a minimum of two well-authenticated cancer cell lines (ideally originating from distinct organs/tissues). For manuscripts dealing with plant extracts or other natural substances/compounds, the composition and the stability of the study material must be described in sufficient detail. In particular, for extracts, chromatograms with characterization of the dominating compound(s) are requested. The level of purity must be proven and included. Please refer to the Four Pillars of Best Practice in Ethnopharmacology, a subset of which concerning general standards in natural product research are applied to all such studies in all sections of Frontiers in Pharmacology.

Many chemotherapeutic agents are available in today’s market that are highly effective against a variety of cancer types; however, the major drawbacks of these chemotherapeutic agents are the many side effects. As an alternative to these chemotherapeutic agents, there are a number of natural agents that are effective against cancer that have been tested in preclinical and clinical models over the years. These natural products must be documented and discussed in order to provide a thorough overview of all the options available for cancer treatment. The Handbook of Research on Natural Products and Their Bioactive Compounds as Cancer Therapeutics emphasizes the list of natural agents against all types of cancers and discusses the current state of research in the fields of natural products and their derivatives against cancer in preclinical and clinical models. This book also provides insight into the applications of meditation and mindfulness-based interventions in clinical and non-clinical conditions. Covering topics such as cancer therapy, antioxidants, and flavonoids, it is ideal for students, research scholars, academicians, professors, scientists, oncologists, doctors, and medical practitioners.

Improving and Accelerating Therapeutic Development for Nervous System Disorders is the summary of a workshop convened by the IOM Forum on Neuroscience and Nervous System Disorders to examine opportunities to accelerate early phases of drug development for nervous system drug discovery. Workshop participants discussed challenges in neuroscience research for enabling faster entry of potential treatments into first-in-human trials, explored how new and emerging tools and technologies may improve the efficiency of research, and considered mechanisms to facilitate a more effective and efficient development pipeline. There are several challenges to the current drug development pipeline for nervous system disorders. The fundamental etiology and pathophysiology of many nervous system disorders are unknown and the brain is inaccessible to study, making it difficult to develop accurate models. Patient heterogeneity is high, disease pathology can occur years to decades before becoming clinically apparent, and diagnostic and treatment biomarkers are lacking. In addition, the lack of validated targets, limitations related to the predictive validity of animal models - the extent to which the model predicts clinical efficacy - and regulatory barriers can also impede translation and drug development for nervous system disorders. Improving and Accelerating Therapeutic Development for Nervous System Disorders identifies avenues for moving directly from cellular models to human trials, minimizing the need for animal models to test efficacy, and discusses the potential benefits and risks of such an approach. This report is a timely discussion of opportunities to improve early drug development with a focus toward preclinical trials.

In the United States, some populations suffer from far greater disparities in health than others. Those disparities are caused not only by fundamental differences in health status across segments of the population, but also because of inequities in factors that impact health status, so-called determinants of health. Only part of an individual's health status depends on his or her behavior and choice; community-wide problems like poverty, unemployment, poor education, inadequate housing, poor public transportation, interpersonal violence, and decaying neighborhoods also contribute to health inequities, as well as the historic and ongoing interplay of structures, policies, and norms that shape lives. When these factors are not optimal in a community, it does not mean they are intractable: such inequities can be mitigated by social policies that can shape health in powerful ways. Communities in Action: Pathways to Health Equity seeks to delineate the causes of and the solutions to health inequities in the United States. This report focuses on what communities can do to promote health equity, what actions are needed by the many and varied stakeholders that are part of communities or support them, as well as the root causes and structural barriers that need to be overcome.

Antibody–drug conjugates (ADCs) represent one of the most promising and exciting areas of anticancer drug discovery. Five ADCs are now approved in the US and EU [i.e., ado-trastuzumab emtansine (Kadcyla™), brentuximab vedotin (Adcetris™), inotuzumab ozogamicin (Besponsa™), gemtuzumab ozogamicin (Mylotarg™) and moxetumomab pasudotox-tdfk (Lumoxiti®)] and over 70 others are in various stages of clinical development, with impressive interim results being reported for many. The technology is based on the concept of delivering a cytotoxic payload selectively to cancer cells by attaching it to an antibody targeted to antigens on the cell surfaces. This approach has several advantages including the ability to select patients as likely responders based on the presence of antigen on the surface of their cancer cells and a wider therapeutic index, given that ADC targeting enables a more efficient delivery of cytotoxic agents to cancer cells than can be achieved by conventional chemotherapy, thus minimising systemic toxicity. Although there are many examples of antibodies that have been developed for this purpose, along with numerous linker technologies used to attach the cytotoxic agent to the antibody, there is presently a relatively small number of payload molecules in clinical use. The purpose of this book is to describe the variety of payloads used to date, along with a discussion of their advantages and disadvantages and to provide information on novel payloads at the research stage that may be used clinically in the future.

The approach to drug discovery from natural sources has yielded many important new pharmaceuticals inaccessible by other routes. In many cases the isolated natural product may not be an effective drug for any of several reasons, but it nevertheless may become a drug through chemical modification or have a novel pharmacophore for future drug design. In summarizing the status of natural products as cancer chemotherapeutics, Anticancer Agents from Natural Products, Second Edition covers the: History of each covered drug—a discussion of its mechanism on action, medicinal chemistry, synthesis, and clinical applications Potential for novel drug discovery through the use of genome mining as well as future developments in anticancer drug discovery Important biosynthetic approaches to "unnatural" natural products Anticancer Agents from Natural Products, Second Edition discusses how complex target-oriented synthesis—enabled by historic advances in methodology—has enormously expanded the scope of the possible. This book covers the current clinically used anticancer agents that are either natural products or are clearly derived from natural product leads. It also reviews drug candidates currently in clinical development since many of these will be clinically used drugs in the future. Examples include the drugs etoposide and teniposide derived from the lead compound podophyllotoxin; numerous analogs derived from taxol; topotecan, derived from camptothecin; and the synthetic clinical candidates, E7389 and HTI-286, developed from the marine leads, halichondrin B and hemiasterlin.

This report is structured in five parts: national framework for traditional and complementary medicine (T&CM); product regulation; practices and practitioners; the challenges faced by countries; and finally the country profiles. Apart from the section on practices and practitioners the report is consistent with the format of the report of the first global survey in order to provide a useful comparison. The section on practices and practitioners which covers providers education and health insurance is a new section incorporated to reflect the emerging trends in T&CM and to gather new information regarding these topics at a national level. All new information received has been incorporated into individual country profiles and data graphs. The report captures the three phases of progress made by Member States; that is before and after the first WHO Traditional Medicine Strategy (1999?2005) from the first global survey to the second global survey (2005?2012) and from the second survey to the most recent timeline (2012?2018).