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.

Predictive drug testing on human tumor cells in order to define the appropriate chemotherapy will remain imperative as long as the anticancer agents available are few in number and show only limited activity. The advantages of an effective test would lie in obviating the need for testing antineoplastic agents on large cohorts of patients for assessment of drug activity (phase II studies) and in allowing determination of optimal use of anticancer agents (phase III trials). Such an in vitro test could help to better define dose and schedule of drugs preclinically. The additive value of individual drugs could be determined on tumor cells in vitro in order to define the best combination chemotherapy in vivo. Test-directed therapy would avoid unnecessary drug-related morbidity in patients with refractory tumors. Chemotherapy treatment would be more than justified even with side effects if palliation or even prolonged survival could be anticipated as a result. The benefits of predictive drug testing on human tumor cells would extend beyond improvement of individual patient treatment if the testing helped to identify new active agents. This spectrum of benefits to the entire field of oncology pro vides tremendous motivation for the development of such testing. Although a number of chemosensitivity tests have been proposed since the advent of modern anticancer chemotherapy, interest has been renewed by the possibility of cloning human tumor cells on agar plates, with a view to testing drug activity on cells with high pro liferation capacity.

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.

A state-of-the art collection of readily reproducible laboratory methods for assessing chemosensitivity in vitro and in vivo, and for assessing the parameters that modulate chemosensitivity in individual tumors. Chemosensitivity,Volume 2: In Vivo Models, Imaging, and Molecular Regulators contains cutting-edge protocols for classifying tumors into response categories and for customizing therapy to individuals. These readily reproducible techniques allow measurements of DNA damage, apoptotic cell death, and the molecular and cellular regulators of cytotoxicity, as well as in vivo animal modeling of chemosensitivity. A companion volume, Volume 1: In Vitro Assays contains in vitro and in vivo techniques to identify which new agents or combination of agents are effective for each type of tumor.

Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.

A FRESH EXAMINATION OF PRECISION MEDICINE'S INCREASINGLY PROMINENT ROLE IN THE FIELD OF ONCOLOGY Precision medicine takes into account each patient's specific characteristics and requirements to arrive at treatment plans that are optimized towards the best possible outcome. As the field of oncology continues to advance, this tailored approach is becoming more and more prevalent, channelling data on genomics, proteomics, metabolomics and other areas into new and innovative methods of practice. Precision Medicine in Oncology draws together the essential research driving the field forward, providing oncology clinicians and trainees alike with an illuminating overview of the technology and thinking behind the breakthroughs currently being made. Topics covered include: Biologically-guided radiation therapy Informatics for precision medicine Molecular imaging Biomarkers for treatment assessment Big data Nanoplatforms Casting a spotlight on this emerging knowledge base and its impact upon the management of tumors, Precision Medicine in Oncology opens up new possibilities and ways of working not only for oncologists, but also for molecular biologists, radiologists, medical geneticists, and others.

Advances in cancer research have led to an improved understanding of the molecular mechanisms underpinning the development of cancer and how the immune system responds to cancer. This influx of research has led to an increasing number and variety of therapies in the drug development pipeline, including targeted therapies and associated biomarker tests that can select which patients are most likely to respond, and immunotherapies that harness the body's immune system to destroy cancer cells. Compared with standard chemotherapies, these new cancer therapies may demonstrate evidence of benefit and clearer distinctions between efficacy and toxicity at an earlier stage of development. However, there is a concern that the traditional processes for cancer drug development, evaluation, and regulatory approval could impede or delay the use of these promising cancer treatments in clinical practice. This has led to a number of effortsâ€"by patient advocates, the pharmaceutical industry, and the Food and Drug Administration (FDA)â€"to accelerate the review of promising new cancer therapies, especially for cancers that currently lack effective treatments. However, generating the necessary data to confirm safety and efficacy during expedited drug development programs can present a unique set of challenges and opportunities. To explore this new landscape in cancer drug development, the National Academies of Sciences, Engineering, and Medicine developed a workshop held in December 2016. This workshop convened cancer researchers, patient advocates, and representatives from industry, academia, and government to discuss challenges with traditional approaches to drug development, opportunities to improve the efficiency of drug development, and strategies to enhance the information available about a cancer therapy throughout its life cycle in order to improve its use in clinical practice. This publication summarizes the presentations and discussions from the workshop.

This book provides a comprehensive, state-of-the-art review of PDX cancer models. In separately produced chapters, the history and evolution of PDX models is reviewed, methods of PDX model development are compared in detail, characteristics of available established models are presented, current applications are summarized and new perspectives about use of PDX models are proposed. Each chapter is written by a world-renowned expert who is conducting cutting-edge research in the field. Each of the subsections provide a comprehensive review of existing literature addressing the particular topic followed by a conclusive paragraph detailing future directions. Extensive illustrations make this an interactive text. Patient-Derived Xenograft Models of Human Cancer will serve as a highly useful resource for researchers and clinicians dealing with, or interested in, this important topic. It will provide a concise yet comprehensive summary of the current status of the field that will help guide preclinical and clinical applications as well as stimulate investigative efforts. This book will propagate innovative concepts and prompt the development of ground-breaking technological solutions in this field.

Of the thousands of novel compounds that a drug discovery project team invents and that bind to the therapeutic target, typically only a fraction of these have sufficient ADME/Tox properties to become a drug product. Understanding ADME/Tox is critical for all drug researchers, owing to its increasing importance in advancing high quality candidates to clinical studies and the processes of drug discovery. If the properties are weak, the candidate will have a high risk of failure or be less desirable as a drug product. This book is a tool and resource for scientists engaged in, or preparing for, the selection and optimization process. The authors describe how properties affect in vivo pharmacological activity and impact in vitro assays. Individual drug-like properties are discussed from a practical point of view, such as solubility, permeability and metabolic stability, with regard to fundamental understanding, applications of property data in drug discovery and examples of structural modifications that have achieved improved property performance. The authors also review various methods for the screening (high throughput), diagnosis (medium throughput) and in-depth (low throughput) analysis of drug properties. - Serves as an essential working handbook aimed at scientists and students in medicinal chemistry - Provides practical, step-by-step guidance on property fundamentals, effects, structure-property relationships, and structure modification strategies - Discusses improvements in pharmacokinetics from a practical chemist's standpoint

Adjuvant treatment is administered prior to or as follow up to surgical procedures for breast cancer. Proven success in using medical therapies allowing for breast conserving procedures or reducing risk of occurrence. Although there has been much progress towards a cure, including the introduction of new targeted therapies, metastasizing cancer remains highly incurable.