With the publication of these proceedings from the Second Drug Discovery and Development Symposium, this forum has become the main mechanism for bringing together the principal groups involved in both discovering and developing new approaches to the treatment of cancer. This Second Symposium emphasized the types of materials being discovered and their therapeutic activity. This is especially evident in the natural product discovery programs, where unique and active structures are being identified. The major contributors to the meeting were the investigators participating in the National Cooperative (Natural Products) Drug Discovery Groups [NC(NP)DDG]. These groups reflect an association among researchers at universities or cancer centers, pharmaceutical companies and the National Cancer Institute. Their sources of materials are varied, reflecting chemical inventories of pharmaceutical companies, organic synthetic compounds from the laboratory, cytotoxics as well as biologics and their hybrids, and natural products obtained from plants, marine organisms and microorganisms. The models employed in the discovery systems vary from broadly cellular based to specific enzymes to defined cellular functions. Each of them is believed important to the malignant state and will allow for the discovery of compounds which will have efficacy in cancer therapy. The goal of the participants is both to discover new anticancer agents and to develop them as efficiently as possible into clinically useful additions to treatment. Of importance is the fact that there are a number of promising leads which will soon be moving into the clinic thereby testing the effectiveness of this NC (NP) DDG approach.

This volume will cover the natural products as they relate to cancer chemotherapy. The topics will include history and current status , recent launches, new clinical candidates and approved drugs directly derived from natural products, current and future cancer target opportunities for natural products, leveraging natural products as tools for new target generation , new approaches to cancer drug discovery through natural products based lead generation, and enabling technologies which leverage the unique attributes of natural products.

Natural products hold a prominent position in the current discovery and development of drugs and have diverse indications for both human and animal health. Plants, in particular, play a leading role as a source of specialized metabolites with medical effects. Other organisms, such as marine and terrestrial animals and microorganisms, produce very important drug candidate molecules. Specialized metabolites from these varied natural sources can be used directly as bioactive compounds or drug precursors. In addition, due to their broad chemical diversity, they can act as drug prototypes and/or be used as pharmacological tools for different targets. Some examples of natural metabolites that have been developed into useful medical drug are cardiotonic digoxin from Digitalis sp., antimalarial artemisinin from Artemisia annua, anti-cancer taxol from Taxus sp., or podophyllotoxin from Podophyllum peltatum, which served as a synthetic model for the anti-cancer etoposide. The study of natural products is still attracting great scientific attention and their current importance, as a valuable lead for drug discovery, is undebatable. I cordially invite authors to contribute original articles, as well as survey articles, that give the readers of Molecules **MOLECULES NEEDS TO BE ITALICIZED** updated and new perspectives on natural products in drug discovery, including but not limited to natural sources, identification and separation of bioactive phytochemicals, standardization, new biological targets, pre-clinical and clinical trials, pharmacological effects/side effects, and bioassays.

This book, Natural Products and Cancer Drug Discovery, is written by leading experts in natural products in cancer therapy. The first two sections describe new applications of common herbs and foods for treatment of cancer. Section 3 deals with the development of new chemotherapeutics from Cannabis and endophytic fungi. Section 4 presented formulations of natural products for treatment of malignant melanoma. Made-to-order anticancer therapy from natural products using computational and tissue engineering approaches is addressed in the fifth section. It is our hope that this book may motivate readers to approach the evidence of anticancer natural products with an open mind and thereby spark an interest in making further contributions to the cancer treatment efforts.

This unique volume traces the critically important pathway by which a "molecule" becomes an "anticancer agent. " The recognition following World War I that the administration of toxic chemicals such as nitrogen mustards in a controlled manner could shrink malignant tumor masses for relatively substantial periods of time gave great impetus to the search for molecules that would be lethal to specific cancer cells. Weare still actively engaged in that search today. The question is how to discover these "anticancer" molecules. Anticancer Drug Development Guide: Preclinical Screening, Clinical Trials, and Approval, Second Edition describes the evolution to the present of preclinical screening methods. The National Cancer Institute's high-throughput, in vitro disease-specific screen with 60 or more human tumor cell lines is used to search for molecules with novel mechanisms of action or activity against specific phenotypes. The Human Tumor Colony-Forming Assay (HTCA) uses fresh tumor biopsies as sources of cells that more nearly resemble the human disease. There is no doubt that the greatest successes of traditional chemotherapy have been in the leukemias and lymphomas. Since the earliest widely used in vivo drug screening models were the murine L 1210 and P388 leukemias, the community came to assume that these murine tumor models were appropriate to the discovery of "antileukemia" agents, but that other tumor models would be needed to discover drugs active against solid tumors.

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.

Plants, marine organisms, and microorganisms have evolved complex chemical defense and signaling systems that are designed to protect them from predators and provide other biological benefits. These organisms thus produce substances containing novel chemotypes that may have beneficial effects for humans. As collection methods improve and new screen