This book presents a comprehensive collection of essential and up-to-date methods for studying both the biology of microtubules and the mechanisms of action of microtubule-interacting drugs. The book contains a straightforward presentation of readily reproducible protocols, tips for troubleshooting, and advice on avoiding common mistakes. Basic scientists and clinical researchers will benefit from this collection.

Cancer drug discovery has been and continues to be a process of ingenuity, serendip ity, and dogged determination. In an effort to develop and discover better therapies against cancer, investigators all over the world have increased our knowledge of cell biology, biochemistry, and molecular biology. The goal has been to define therapeuti cally exploitable differences between normal and malignant cells. The result has been an increased understanding of cellular and whole-organism biology and an increased respect for the flexibility and resiliency ofbiologically systems. Thus, as some new therapeutic targets have been defined and new therapeutic strategies have been attempted, so have some new biological hurdles resulting from tumor evasion of the intended therapeutic attack been discovered. Historically, anticancer drugs have originated from all available chemical sources. Synthetic molecules from the chemical industry, especially dyestuffs and warfare agents, and natural products from plants, microbes, and fungi have all been potential sources of pharmaceuticals, including anticancer agents. There is no shortage of molecules; the challenge has been and continues to be methods of identifying molecules that have the potential to be therapeutically important in human malignant disease. "Screening" remains the most important and most controversial method in cancer drug discovery. In vitro screens have generally focused on cytotoxicity and have identified several highly cytotoxic molecules. Other endpoints available in vitro are inhibition of proliferation, 3 inhibition of [ H]thymidine incorporation into DNA and various viability assays, based most frequently on dye exclusion or metabolism.

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 1: In Vitro Assays provides a panel of 16 in vitro measures of chemosensitivity in adherent and non-adherent cells for single agents and combinations of agents. In addition to immunohistochemical and imaging approaches, these assays include clonogenic, colorimetric, fluorometric, and physiological assays. Highlights include image analysis to assess drug sensitivity, high throughput approaches using green fluorescent protein, DIMSCAN (a microcomputer fluorescence-based assay), and the ChemoFx assay used in biotechnology. A companion volume, Volume 2: In Vivo Models, Imaging, and Molecular Regulators, provides protocols for classifying tumors into response categories and customizing chemotherapy regimens to individual patients.

This volume commemorates the 30th anniversary of the discovery in 1971 of the first DNA topoisomerases, i.e topoisomerase I in E. coli, then provisionally named omega' protein, by the pioneering work of Jim Wang at Harvard University, who has contributed an article to this volume: Reflections on an accidental discovery' of the enzyme. Many kinds of topoisomerase have since been found from type I through to type VI in a variety of organisms ranging from viruses to higher eukaryote mammals. The wide distribution of enzymes in various forms of life implies that the DNA topoisomerase is essential for life.

In the mid 80's type I and II enzymes were found to be the intracellular targets of a number of efficacious anticancer drugs such as doxorubicin, mitoxantrone, etoposide and camptothecin as a result of a continued efforts of many investigators, especially Leroy Liu and his collaborators at Johns Hopkins University. Readers will find a series of chapters written by researchers actively engaged in the expanding field of topoisomerase and their inhibitors. The series of chapters cover review articles on pharmacology and the molecular mechanism of topoisomerase I- and II-targeting anticancer drugs in mammals and in the yeast Saccharomyces cerevisiae, which has proved to be a superb model organism for studies of anticancer drugs. This volume compiles up-to-date information on the topoisomerase-targeting compounds in clinical and preclinical development as a useful and important reference book for students and researchers in the field of pharmacology, toxicology, oncology and molecular biology.

This collection of thoughtful and provocative articles focused on the key issues in apoptosis, ranges from the role of apoptosis in defining the response of authentic tumor populations to chemotherapeutic agents to the mechanisms coupling DNA damage to the activation pathway of apoptosis. It reviews the profusion of new signaling, modulating, and effector molecules now implicated in apoptosis and whether other routes to "programmed" cell death may exist. Also addressed are the nature of the molecules that will either constitute targets for future drugs or influence the efficacy of current therapies, as well as mechanistic questions on the control of apoptosis. By focusing on essential questions and critically summarizing the overwhelming tide of recent research results, Apoptosis and Cancer Chemotherapy illuminates not only the potential targets for tumor therapy, but beyond that, potential control points for cancer and such diverse diseases as viral infection, neurodegenerative disorders, and stroke. This collection of cutting-edge reviews by established leaders in the field critically summarizes the recent discoveries concerning apoptosis, cell suicide. The book looks forward to the time when such cell death can be controlled to treat cancer and a host of other diseases as diverse as viral infection, neurodegenerative disorders, and stroke.

In Targets for Cancer Chemotherapy: Transcription Factors and Other Nuclear Proteins, a panel of leading basic researchers, pharmaceutical scientists, and clinical oncologists explain in detail the therapeutically-relevant protein targets that contribute to cancer pathology and spell out their implications for cancer drug discovery and clinical application. The authors identify and illuminate selected transcription factor oncoproteins and tumor suppressors, together with nuclear proteins that are central to the phenotype of the tumor cell involved in chromatin control. The emphasis is on new targets and approaches to cancer treatment derived from the cancer cell cycle, gene control targets, and angiogenesis.

The growth in chemotherapy has led to a great need for all those involved to be familiar with safe procedures based on best evidence-based practice. Practical Chemotherapy: a multidisciplinary guide is a comprehensive and straightforward guide describing over 70 widely used chemotherapy regimens, helping to make their prescription and administration safer and less problematic. Checklists throughout the book are specifically tailored for the needs of each professional group involved in treatment, and are intended to help prevent potentially serious mistakes that can occur. This book is unique in its practical emphasis and will be invaluable for doctors, pharmacists and nurses working in oncology and haematology.

Over the last decade, cytokine research has emerged as one of the most exciting and critical fields for providing fundamental knowledge of normal and abnormal human development. Today, it is apparent that cytokines orchestrate growth from the early embryonic stage to maturity and are responsible for the normal function of virtually every organ system. Furthermore, virtually all disease states have been associated, at least in part, with cytokine aberrations. In this volume, the editors have brought together internationally known experts in the field of interleukin research to provide a comprehensive review of the biology of the interleukins and their role in both health and illness, while maintaining a balance between the basic science and clinical aspects. Cytokines: Interleukins and their Receptors should be of interest to a wide variety of researchers including clinical hematologists, oncologists, immunologists, in addition to medical and PhD students and researchers with an interest in cytokines.

Over the last 50 years, drug development and clinical trials have resulted in successful complete responses in diseases such as childhood leukemia, testicular cancer and Hodgkin's disease. We are still, however, confronted with over 500,000 cancer-related deaths per year. Clearly, the phenomenon of drug resistance is largely responsible for these failures and continues to be an area of active investigation. Since the last volume in this series, we have learned that the energy-dependent drug efflux protein, p-glycoprotein, encoded by the MDR 1 gene, is a member of a family of structurally related transport polypeptides, thus allowing us to explore the relationship between structure and function. In addition to ongoing well designed clinical trials aimed at reversing MDR mediated drug resistance, the first gene therapy studies with the MDR 1 gene retrovirally transduced into human bone marrow cells are about to be initiated. Although MDR is currently the most understood mechanism of drug resistance, we are uncovering increasing knowledge of alternative molecular and biochemical mechanisms of drug resistance to antimetabolites, cisplatin and alkylating agents and developing new strategies for circumventing such resistance. It is clear that drug resistance is complex, and many mechanisms exist by which cancer cells may overcome the cytotoxicity of our known chemotherapeutic agents. As our understanding of each of these mechanisms expands, well designed models will be necessary to test laboratory hypotheses and determine their relationship to drug resistance in humans. It is this integration of basic science and clinical investigation that will both advance our scientific knowledge and result in the improvement of cancer therapy.

This handbook is a concise, thorough, and portable reference guide to the multitude of complex chemotherapy protocols and other frequently utilized medications in the field of Hematology/Oncology. Its inclusion of commonly used oncology regimens, guidelines for supportive care during administration and sections on pain control, antibiotic use and antiemesis guidelines set it apart from other "chemotherapy handbooks". The authors have prepared this book with the intention of improving the care of those suffering from cancer.

Cutting-edge researchers describe their efforts to design, synthesize, and evaluate the biological activities of farensyltransferase inhibitors (FTIs); geranylgeranyltransferase inhibitors (GGTIs) are also discussed as potential anticancer drugs. The authors survey in detail such inhibitors as CAAX box peptidomimetics, FPP mimics, and bisubstrate transition state analogs, and critically review their uses in combination with radiation and other cytotoxic agents, such as gemcitabine, cisplatin, and taxanes. Illuminating and richly detailed, Farnesyltransferase Inhibitors in Cancer Therapy constitutes today's standard reference for the pathbreaking use of FTIs and GGTIs in anticancer therapy and offers basic and clinical investigators a comprehensive treatment of the scientific and medical aspects of farnesyltransferase inhibitors.

Maurie Markman and a panel of distinguished clinicians and leading clinical investigators comprehensively review the current status of regional antineoplastic drug delivery in the management of malignant disease. These authorities present a critical analysis of both the rationale and limitations of regional therapy and discuss potential clinical trials designed to explain the effectiveness of this method of therapy in special settings. Their presentations describe many exciting and innovative strategies for using regional drug delivery in anticancer therapy, including coverage of such areas of special interest as colorectal, skin, lung, pancreatic, ovarian, and gastrointestinal cancers. Comprehensive and authoritative, Regional Chemotherapy: Clinical Research and Practice offers surgical and medical oncologists and clinical cancer investigators a gold-standard review of the current role and future development of this increasingly powerful weapon in the battle against cancer.

Nausea and vomiting are two of the most common side-effects of anti-cancer treatment, and the discovery and clinical application of 5-hydroxytryptamine3 receptor antagonists has transformed the management of these side effects, resulting in a much improved quality of life for cancer patients. This text presents a detailed overview of the management of cancer-treatment induced emesis in a number of different treatment settings, and focuses on the mechanisms and use of 5-HT3 receptor antagonists. Contributions are also included from the points of view of the nurse and the patient.

Cytokines in the Genesis and Treatment of Cancer provides a comprehensive picture of the dual role of host responses in promoting and inhibiting tumor progression. This volume represents an important investigation into the emerging intersection of cancer biology and cancer immunology. The book brings together an impressive array of internationally distinguished investigators who are devoted to the study of cytokines and cancer.

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.

Students and house staff officers are lucky when one of their professors takes the time to discuss with them how he/she tells a bad diagnosis to a new patient. This is how I advise them to handle it: 'Take a chair or sit on the edge of the bed if need be and touch a hand. That will comfort the patient. And don't think for a minute that men do not appreciate that gesture; they do. Unless the patient decides differently, it is better when the spouse, a close member of the family or a friend is present. Remember that after you leave the room, it will be awfully lonely for the patient. Tell the bad news, but immediately hold out a few rays of hope to grasp. And be prepared to answer the questions that will follow, not once but several times because most patients do not remember what you told them. You will be amazed how the well-informed patients accept the worst diagnosis and how grateful they are that you took the time to sit with them. Answer all questions and remember, the informed patient becomes your best patient. And no question is a dumb question.'

Concepts, Mechanisms, and New Targets for Chemotherapy describes new interconnections between rationally designed and empirically discovered compounds. One route that has not been travelled previously is that of protein kinase C inhibition. This pathway may be exploited to give potent inhibitors, such as the bryostatins, now in clinical trial. A summary is given of the current status of topoisomerase, focusing on recent clinical advances with camptothecin analogs based on connecting empiricism with concepts of drug selectivity. Modification of existing therapies based on the pursuit of leads arising from mechanistic studies is also being applied clinically on a wide scale. Greater understanding should follow from the studies of reversal of the multidrug resistant phenotype, on the use of hydroxyurea to reverse resistance mediated by extrachromosomal DNA, and on various aspects of the fluoropyrimidine pathways. Successful applications of chemotherapy to the treatment of specific diseases include the growing applications of systemic therapy using various skin malignancies. In prostate cancer, estramustine phosphate will likely play an expanding role. Taxanes are restructuring treatment regimens in breast cancer, and high-dose strategies are described with peripheral blood progenitor autografting in the treatment of ovarian and breast cancers.

Resistance to treatment represents the final common outcome for far too many patients with cancer. Even our most promising new drugs fall victim to drug resistance. Hormones and newer biological therapies, though safe and active, also lose their activity over time. In this volume of Drug Resistance, leading investigators in the field have reviewed the most basic mechanisms of drug resistance, and have proposed ways to modulate resistance. This comprehensive volume should be of value for basic and clinical scientists who wish to delve more deeply into this intriguing problem in the laboratory and devastating problem in the clinic.

Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.

Principles of Clinical Cancer Research provides comprehensive coverage of the fundamentals of clinical cancer research, including the full spectrum of methodologies used in the field. For those involved in research or considering research careers, this book offers a mix of practical advice and analytical tools for effective training in theoretical principles as well as specific, usable teaching examples. The clinical oncologist or trainee will find a high-yield, practical guide to the interpretation of the oncology literature and the application of data to real-world settings. Valuable for both researchers and clinicians who wish to sharpen their skills, this book contains all the cornerstones and explanation needed to produce and recognize quality clinical science in oncology.Written from the physician-scientist's perspective, it lays a strong foundation in pre-clinical sciences that is highly relevant to careers in translational oncology research along with coverage of population and outcomes research and clinical trials. It brings together fundamental principles in oncology with the statistical concepts one needs to know to design and interpret studies successfully. With each chapter including perspectives of both clinicians and scientists, Principles of Clinical Cancer Research provides balanced, instructive, and high-quality topic overviews and applications that are accessible and thorough for anyone in the field. Key Features: Gives real-world examples and rationales behind which research methods to use when and why Includes numerous tables featuring key statistical methods and programming commands used in everyday clinical research Contains illustrative practical examples and figures in each chapter to help the reader master the main concepts Provides tips and pointers for structuring a career, avoiding pitfalls, and achieving success in the field of clinical cancer research Access to fully downloadable ebook

Peritoneal dissemination is a common route of cancer metastasis. The benefit of administering chemotherapy directly into the peritoneal cavity is supported by preclinical and pharmacokinetic data. In comparison to intravenous (IV) treatment, intraperitoneal (IP) administration results in a several-fold increase in drug concentration within the abdominal cavity. There is now growing evidence from clinical studies showing a survival advantage for IP chemotherapy in various tumor typies, including ovarian, gastric and colorectal cancer. However, while the use of IP chemotherapy is slowly gaining acceptance, it is not universal, largely due to the greater toxicity associated with this approach. Moreover, efficacy of IP chemotherapy is limited by poor distribution within the abdominal cavity and by poor tissue penetration. A new way of IP chemotherapy is the application of cytotoxics in form of a pressurized aerosol into the abdominal of thoracic cavity. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is applied through laparoscopic access using two balloon trocars in an operating room equipped with laminar air-flow. In a first step,a normothermic capnoperitoneum is established with a pressure of 12 mmHg. A cytotoxic solution (about 10% of a normal systemic dose) is nebulized with a micropump into the abdominal cavity, and maintained for 30 min. The aerosol is then removed through a closed suction system. Applying an aerosol in the peritoneal cavity allows a homogeneous distribution of the chemotherapeutic agent within the abdomen. Furthermore, an artificial pressure gradient is generated that overcomes tumoral interstitial fluid pressure, an obstacle in cancer therapy. This results in a higher local drug concentration compared to conventional IP or IV chemotherapy. At the same time the plasma concentration of the chemotherapeutic agent remains low. In first clinical studies with limited number of patients in ovarian, gastric and colorectal cancer, as well as peritoneal mesothelioma, PIPAC has obtained encouraging tumor response rates and survival, with a low-side effects profile. Larger clinical trials are currently ongoing to examine if these data can be reproduced and extrapolated to other situations.

Updated and expanded, this Second Edition of Essentials of Clinical Radiation Oncology continues to provide a succinct and effective review of the most important studies in the field. Organized by disease topic and grouped by body part, each chapter employs structured sections for targeted information retrieval and retention. Chapters begin with a "Quick Hit" overview of each disease summarizing the most significant paradigms before moving into dedicated summaries on epidemiology, risk factors, anatomy, pathology, genetics, screening, clinical presentation, workup, prognostic factors, staging, treatment paradigm, and medical management. An evidence-based question and answer section concludes each chapter, which pairs commonly encountered clinical questions with answers connecting historical context and pertinent clinical studies to better inform decision making and treatment planning.Providing the latest treatment paradigms and guidelines, this comprehensive second edition now outlines the evidence and must-know considerations for using radiation therapy with immunotherapy, the strategies for metastasis-directed therapy for oligometastatic disease, and much more. Written for the practicing radiation oncologist, related practitioner, and radiation oncology resident entering the field, this "one-stop" resource is the go-to reference for everyday practice. Key Features: Structured sections offer high-yield information for targeted review Cites need-to-know clinical studies and treatment guidelines in evidence-based question and answer format Each chapter has been reviewed and updated to include the most recent and relevant studies New chapters on spine tumors, thyroid cancer, sinonasal tumors, cholangiocarcinoma, renal cell carcinoma, multiple myeloma and plasmacytoma, miscellaneous pediatric tumors, and treatment of oligometastatic disease from underlying cancers Designed for quick reference with comprehensive tables on treatment options and patient selection, workup, and prognostic factors by disease site Purchase includes digital access for use on most mobile devices or computers

There is now a range of cytotoxic drugs that have considerable clinical usefulness in producing responses in tumors and even, in a small proportion of cases, cure. However, the acquisition of drug resistance is a major clinical problem and is perhaps the main limiting factor in successful treatment of cancer. Thus, a tumor initially sensitive to chemotherapy will, in the majority of cases, eventually recur as a resistant tumor, which will then progress. Much of our understanding of drug resistance mechanisms comes from the study of tumor cell lines grown in tissue culture. We now understand many of the - lecular mechanisms that can lead to a cell acquiring resistance to antic- cer drugs; however, we still do not know which mechanism(s) are those most relevant to the problem of clinical drug resistance. Indeed, given that many of the cytotoxic anticancer drugs were discovered by random screening, it is - clear what features give a clinically useful anticancer drug a sufficient the- peutic index to be of value. The aim of Cytotoxic Drug Resistance Mechanisms is to provide pro- cols that are appropriate for examining the mechanisms of cellular resistance to anticancer cytotoxics in human tumor samples. Tumor cell lines have been enormously useful as experimental models of drug resistance mechanisms, however they have limitations and we need to address the relevance of such mechanisms in patients' tumors. Examining drug resistance in tumors is much more problematic than in cell lines.

This book presents an overview of the development of targeted therapies for the treatment of cancer with an emphasis on clinical application. The volume covers the complexity of the rapidly developing area of targeted therapies for the treatment of patients with cancer. It is structured in a way so readers may begin with chapters that most interest them and work through the rest of the chapters in the order of their choice.

App included with purchase! See inside front cover for access instructions. Radiation Oncology Board Review with Flashcard App efficiently tests and reinforces your knowledge of key concepts, critical studies, and major clinical guidelines, with the most important radiation oncology citations included. Organized by treatment site, detailed questions cover natural history, epidemiology, diagnosis, staging, treatment options, and treatment-related side effects all in a newly configured format. Each question tests your recall and sharpens your skills so that you can practice and feel confident in your ability to manage all disease site areas according to the standard guidelines and key literature in the field. This updated second edition to Radiation Oncology Self-Assessment Guide also includes a companion flashcard app, so you can easily access and navigate over 950 questions on a smartphone, tablet or desktop computer. Written by residents and expert radiation oncologists from the Cleveland Clinic Taussig Cancer Institute, this review is a comprehensive study guide for anyone preparing for the board exam, for practicing physicians reviewing a topic, or preparing for MOC. Whether you are a few minutes between patients or are having a dedicated study session, this book and app bundle is an invaluable resource that will strengthen your knowledge of the field. Key Features: Updated and revised to reflect the new AJCC 8th Edition criteria, data guidelines for SBRT, hypofractionation for breast and prostate cancers, new advanced treatment planning and delivery techniques, and a dedicated Sarcomas section Covers all clinical topics and disease site areas that are in the ABR clinical radiation oncology exam and MOC Updated flashcard layout and organization of questions and answers Includes free access to mobile and online app-track and sync your progress on up to three devices!