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.

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.

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!

Glioblastoma Resistance to Chemotherapy: Molecular Mechanisms and Innovative Reversal Strategies brings current knowledge from an international team of experts on the science and clinical management of glioblastoma chemoresistance. The book discusses topics such as molecular mechanisms of chemoresistance, experimental models to study chemoresistance, chemoresistance to drugs other than Temozolomide, and specific strategies to reverse chemoresistance. Additionally, it encompasses information on how to mitigate chemoresistance by targeted enhancement of p53 function. This book is a valuable resource for cancer researchers, oncologists, neuro-oncologists and other members of the biomedical field. Glioblastoma (GBM) is the most invasive and malignant primary brain tumor in humans with poor survival after diagnosis, therefore it is imperative that molecular and cellular mechanisms behind therapy resistant GBM cells, as well as the therapeutic strategies available to counter the resistance are comprehensively understood.

Waterborne Pathogens: Detection Methods and Applications, Second Edition, gives an overview of advanced and emerging technologies in the detection of a range of waterborne pathogens. In addition, the book presents existing methodologies, highlights where improvements can be made, includes applications, and touches on the ways in which new technologies can be applied in water management. Finally, the book addresses issues of sample preparation (from sampling, to concentration and enrichment), a key stage in any detection protocol.

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.

Tyrosine Kinase Inhibitors as Sensitizing Agents for Chemotherapy, the fourth volume in the Cancer Sensitizing Agents for Chemotherapy Series, focuses on strategic combination therapies that involve a variety of tyrosine kinase inhibitors working together to overcome multi-drug resistance in cancer cells. The book discusses several tyrosine kinase inhibitors that have been used as sensitizing agents, such as EGFR, BCR-ABL, ALK and BRAF. In each chapter, readers will find comprehensive knowledge on the inhibitor and its action, including its biochemical, genetic, and molecular mechanisms' emphases. This book is a valuable source for oncologists, cancer researchers and those interested in applying new sensitizing agents to their research in clinical practice and in trials.

The introduction of new anticancer drugs and drug combinations, as well as the use of high-dose chemotherapy with growth factor and hemopoietic stem cell support, has greatly increased clinical remission rates. Unfortunately palliation, rather than cure, remains the most realistic goal of chemotherapy for many patients. The failure to cure metastatic cancer is commonly attributed to drug "resistance." Resistance can be broadly viewed as the survival of malignant cells because of a failure to deliver an effective drug dose to the (cellular) target, resulting from any one of or combination of individual factors. For example, inter-individual genetic differences in drug metabolism, as well as differences in tumor kinetics and vascularization, may be important for treatment outcome. In addition, numerous molecular mechanisms of resistance have been elucidated at the level of the individual tumor cell.
The present volume reviews clinically relevant aspects of the pharmacokinetics of commonly used anticancer agents as well as mechanisms of cellular/experimental resistance to such agents. This extends to technological advances that enable high-throughput studies of genetic polymorphisms, which has opened up new avenues to the study of drug resistance and to the individualization of chemotherapy in order to decrease clinical toxicity and optimize treatment results.
"This text provides a comprehensive review of the mechanisms of resistance to cancer chemotherapuetic agents. Leading experts discuss molecular and biochemical pathways that influence cytotoxicity. Knowledge of these potential obstacles to therapy will allow for the development of more effective strategies to treat malignantdiseases."
Steven T. Rosen, M.D., Series Editor

We are in an exciting era in the war against cancer, with real prospects for novel anticancer drugs that are cancer cell-specific without the toxicities that have been the hallmark of conventional cytotoxic cancer chemotherapy. Advances in cancer cell biology fueled by the molecular biology revolution have resulted in the uncovering of many novel potential molecular targets for cancer therapy. New anticancer drug discovery and development is now largely focused on exploiting these new molecular targets, which encompass oncogenes, tumor s- pressor genes, and their gene products, as well as targets involved in tumor angiogenesis, metastasis, survival, and longevity mechanisms. Exploitation of some of these targets has already yielded fruits and introduced new paradigms of molecularly targeted cancer therapy into the clinic, namely, protein kinase in- bition by antibodies or small molecules, exemplified by Herceptin (R) (trastuzumab), a humanized antibody targeted against the HER-2 growth factor receptor tyrosine kinase for the treatment of metastatic breast cancer; and Gleevec, a small molecule bcr-abl kinase inhibitor for the treatment of chronic myel- enous leukemia.

Leading international experts comprehensively review all aspects of platinum anticancer drugs and their current use in treatment, as well as examining their future therapeutic prospects. Writing from a variety of disciplines, these authorities discuss the chemistry of cisplatin in aqueous solution, the molecular interaction of platinum drugs with DNA, and such exciting new areas as DNA mismatch repair and replicative bypass, apoptosis, and the transport of platinum drugs into tumor cells. The emergent platinum drugs of the future-orally active agents, the sterically hindered ZD0473, and the polynuclear charged platinum BBR3464-are also fully considered. Timely and interdisciplinary, Platinum-Based Drugs in Cancer Therapy offers cancer therapeutics specialists an illuminating survey of every aspect of platinum drugs from mechanisms of action to toxicology, tumor resistance, and new analogs.

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.

Intraperitoneal Cancer Therapy: Principles and Practice is one of the first books to combine the latest clinical developments in the treatment of patients with peritoneal surface disease and the scientific principles that underlie the concept of intraperitoneal cancer therapy. The book covers basic concepts such as anatomy, physiology, pharmacology, and mathematical models of drug transport as well as practical clinical applications, highlighted with results from clinical trials and promising novel preclinical developments. The book is a state-of-the-art reference for surgical and medical oncologists interested in the treatment of carcinomatosis. It also establishes and promotes basic and translational research interest in the field of intraperitoneal drug delivery, which has the potential to improve the outcome for this dreaded condition. Edited by two renowned surgical oncologists, it represents the definitive reference in the field of intraperitoneal cancer therapy.

A guide to state-of-the-art cancer immunotherapy in translational cancer research A volume in the Translational Oncology series, Immunotherapy in Translational Cancer Research explores the recent developments in the role that immunotherapy plays in the treatment of a wide range of cancers. The editors present key concepts, illustrative examples, and suggest alternative strategies in order to achieve individualized targeted therapy. Comprehensive in scope, Immunotherapy in Translational Cancer Research reviews the relevant history, current state, and the future of burgeoning cancer-fighting therapies. The book also includes critical information on drug development, clinical trials, and governmental resources and regulatory issues. Each chapter is created to feature: development of the immunotherapy; challenges that have been overcome in order to scale up and undertake clinical trials; and clinical experience and application of research. This authoritative volume is edited by a team of noted experts from MD Anderson Cancer Center, the world's foremost cancer research and care center and: Offers a comprehensive presentation of state-of-the-art cancer immunotherapy research that accelerates the pace of clinical cancer care Filled with the concepts, examples, and approaches for developing individualized therapy Explores the breath of treatments that reflect the complexity of the immune system itself Includes contributions from a panel international experts in the field of immunotherapy Designed for physicians, medical students, scientists, pharmaceutical executives, public health and public policy government leaders and community oncologists, this essential resource offers a guide to the bidirectional interaction between laboratory and clinic immunotherapy cancer research.

This timely new reference integrates the latest clinical results and laboratory studies on the resistance of specific cancers to chemotherapeutic drugs-covering drug resistance in lung, breast, ovary, and colon cancer as well as hematological malignancies.

Microspheres and Regional Cancer Therapy takes an interdisciplinary approach to the subject of microspheres and regional cancer therapy. It synthesizes laboratory and clinical data to demonstrate the utility of microsphere-based strategies in the treatment of localized solid tumors (particularly in the liver) not amenable to surgery and as a component of strategies for treatment of disseminated disease. Using the same techniques that show the deficiencies of delivery strategies involving antibodies, liposomes, and synthetic polymers, clear evidence is presented describing how microspheres of appropriate size can be localized in solid tumor deposits in the liver with little exposure to other organs. To exploit this phenomenon, the extent and nature of the incorporation of active agents within microspheres is discussed in relation to release, pharmacokinetics, and tumor response achieved by intensification of therapy in the manner described. This book will benefit laboratory-based scientists and clinicians in pharmaceutics, pharmacology, physiology, surgical oncology, and nuclear medicine. In addition, cancer clinicians interested in the value of regional therapy will be able to evaluate the underlying theory and learn the necessary methodology.

Bodies Unbound is a comparative study showing how ideologies of gendered bodies shape medical care and the ways in which patients respond to these ideologies through decisions about their bodies using three cases: transgender men seeking preventative gynecological care, cisgender men diagnosed with breast cancer, and cisgender women with breast cancer who elect to undergo prophylactic mastectomies. Bodies Unbound is a story about how the relationship between bodies and gender becomes socially intelligible as well as how medical professionals use their position of relative authority over bodies to dictate which combinations of bodies and genders are legitimate or not. Drawing on the experiences of individuals whose bodies and gender identities don't match medical and social expectations for gynecological and breast cancer care, Sledge unravels the taken-for-granted alignment of bodies and gender that provide the foundation of medical care in the United States. 

Covering all aspects of photodynamic therapy, 70 expert contributors from the fields of photochemistry, photobiology, photophysics, pharmacology, oncology and surgery, provide multidisciplinary discussions on photodynamic therapy - a rapidly-developing approach to the treatment of solid tumours.;Photodynamic Therapy: Basic Principles and Clinical Applications describes the molecular and cellular effects of photodynamic treatment; elucidates the complex events leading to photodynamics tissue destruction, particularly vascular and inflammatory responses; discusses the principles of light penetration through tissues and optical dosimetry; examines photosensitizer pharmacology and delivery systems; reviews in detail photosensitizer structure-activity relationships; illustrates novel devices that aid light dosimetry and fluorescence detection; and extensively delineates clinical applications, including early diagnosis and treatment.;A comprehensive and up-to-date reference, this book should be useful for oncologists, pharmacologists, surgeons, photobiologists, optical engineers, laser technicians, biologists, physicists, chemists and biochemists involved in cancer research, as well as graduate-level students in these disciplines.

Named after Selene, Greek goddess of the moon, selenium (Se) has moved has moved from being thought of as a toxicant to being considered an essential nutrient with the potential to reduce cancer risk in the span of seven decades. Diversity of Selenium Functions in Health and Disease focuses on current knowledge of aspects of Se research relevant to its medical use, and particularly to chemoprevention of cancer. It covers how Se is integrated into selenoproteins, selenium compounds with individual functions and dual functions, and unexpected links to Se such as with diabetes. The text ends with a discussion of polymorphisms and mutations in genes of selenoproteins. The chapters elucidate why studies undertaken to prevent diseases with selenium ended with disappointing outcomes and often with the opposite result, i.e. disease promotion. They show that benefit, failure, or side effects depend on: The chemical form and dose of selenium The selenium status of the individual ingesting selenium The capacity of selenium form to serve as a source for selenoprotein biosynthesis The function of selenoproteins reacting to a change in the selenium status The stage of the disease (mainly cancer) at the time point of intervention The genetic background of individuals to be treated Bringing together the accumulated evidence regarding selenium biochemistry, the book covers aspects not found in available general monographs. The narrow focus on medical uses of Se helps resolve the present confusion about potential benefits and hazards of selenium in human health. The book gives you a solid scientific basis for optimum use of selenium in preventing or treating human diseases and answering the questions: Why is selenium essential? How much is required? What are the health consequences of low selenium and can selenium reduce cancer risk?

There have been tremendous recent advances in the pharmacotherapy, dose regimens, and combinations used to treat cancer and for the treatment or prevention of the spread of disease. As a direct result of these advances, there are an increasing number of cancer survivors, although research dealing with chemotherapy-induced pain is still in its early years.

Written for pain management specialists, oncologists, pharmacologists, students, and primary care practitioners, Chemotherapy-Induced Neuropathic Pain provides insight into the important area of chemotherapy-induced neuropathic pain. It reviews the basic and clinical research into the normal physiology of pain transmission pathways, neuropathic pain pathology, the chemotherapeutic drug mechanisms of action and adverse effects, chemotherapy-induced neuropathy, and drug discovery efforts for treatment.

The contributors comprise an impressive list of clinical and basic science experts in the fields of pain mechanisms and pain management. Included are clinical directors of pain clinics and clinical research facilities, directors of large academic pain research laboratories, analgesic drug developers, and presidents of the International Association for the Study of Pain (IASP), Association of Chronic Pain Patients (ACPP), and the British Pain Society (BPS). Through them, the book provides the reader with an exceptional opportunity to acquire a fundamental understanding of the basic concepts related to this topic.

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