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Chemotherapy is one of the major treatment options for cancer patients; however, the efficacy of chemotherapeutic management of cancer is severely limited by multidrug resistance, in that cancer cells become simultaneously resistant to many structurally and mechanistically unrelated drugs. In the past three decades, a number of mechanisms by which cancer cells acquire multidrug resistance have been discovered. In addition, the development of agents or strategies to overcome resistance has been the subject of intense study. This book contains comprehensive and up-to-date reviews of multidrug resistance mechanisms, from over-expression of ATP-binding cassette drug transporters such as P-glycoprotein, multidrug resistance-associated proteins, and breast cancer resistance p- tein to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The book also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression. In addition, this book contains techniques for the detection and imaging of drug transporters, methods for the investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. The book intends to provide a state-of-the-art collection of reviews and methods for both basic and clinician investigators who are interested in cancer multidrug resistance mechanisms and reversal strategies. Tianjin, China Jun Zhou v Contents Preface. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Contributors. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix 1 Multidrug Resistance in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Bruce C. Baguley 2 Multidrug Resistance in Oncology and Beyond: From Imaging of Drug Efflux Pumps to Cellular Drug Targets . . . . . . . . . . . . . . . . . . . . . . . . . .
Drug Resistance in Colorectal Cancer: Molecular Mechanisms and Therapeutic Strategies, Volume Eight, summarizes the molecular mechanisms of drug resistance in colorectal cancer, along with the most up-to-date therapeutic strategies available. The book discusses reasons why colorectal tumors become refractory during the progression of the disease, but also explains how drug resistance occurs during chemotherapy. In addition, users will find the current therapeutic strategies used by clinicians in their practice in treating colorectal cancer. The combination of conventional anticancer drugs with chemotherapy-sensitizing agents plays a pivotal role in improving the outcome of colorectal cancer patients, in particular those with drug-resistant cancer cells. From a clinical point-of-view, the content of this book provides clinicians with updated therapeutic strategies for a better choice of drugs for drug-resistant colorectal cancer patients. It will be a valuable source for cancer researchers, oncologists and several members of biomedical field who are dedicated to better treat patients with colorectal cancer.
Holland-Frei Cancer Medicine, Ninth Edition, offers a balanced view of the most current knowledge of cancer science and clinical oncology practice. This all-new edition is the consummate reference source for medical oncologists, radiation oncologists, internists, surgical oncologists, and others who treat cancer patients. A translational perspective throughout, integrating cancer biology with cancer management providing an in depth understanding of the disease An emphasis on multidisciplinary, research-driven patient care to improve outcomes and optimal use of all appropriate therapies Cutting-edge coverage of personalized cancer care, including molecular diagnostics and therapeutics Concise, readable, clinically relevant text with algorithms, guidelines and insight into the use of both conventional and novel drugs Includes free access to the Wiley Digital Edition providing search across the book, the full reference list with web links, illustrations and photographs, and post-publication updates
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 explains the pharmacological relationships between the various systems in the human body. It offers a comprehensive overview of the pharmacology concerning the autonomic, central, and peripheral nervous systems. Presenting up-to-date information on chemical mediators and their significance, it highlights the therapeutic aspects of several diseases affecting the cardiovascular, renal, respiratory, gastrointestinal, endocrinal, and hematopoietic systems. The book also includes drug therapy for microbial and neoplastic diseases. It also comprises sections on immunopharmacology, dermatological, and ocular pharmacology providing valuable insights into these emerging and recent topics. Covering the diverse groups of drugs acting on different systems, the book reviews their actions, clinical uses, adverse effects, interactions, and subcellular mechanisms of action. It is divided into 11 parts, subdivided into several chapters that evaluate the basic pharmacological principles that govern the different types of body systems. This book is intended for academicians, researchers, and clinicians in industry and academic institutions in pharmaceutical, pharmacological sciences, pharmacy, medical sciences, physiology, neurosciences, biochemistry, molecular biology and other allied health sciences.
This book aims to describe the current state of knowledge and possible future developments in a number of major areas of research into the nature, causes and treatment of cancer. The contributing authors have been encouraged to discuss their subjects at the molecular level. It will become apparent to the reader that considerable developments in the understanding of the fundamental nature of cancer, in molecular terms, are constantly being made. This is particularly the case in the area of oncogene research where differences between tumour and normal cells can now be defined in terms of altered expression of DNA sequences. An understanding of the methods available for detecting cancer, of the process of carcinogenesis and of the means available for treating cancer can only be achieved with a precise knowledge of the basic biochemical and molecular processes involved. Since it is all to easy for the research scientist to become totally absorbed within the specialised area of research in which he is involved, the first chapter is an attempt to encourage a broader field of vision by introducing the clinician's view of the cancer problem, which illustrates the broad spectrum of basic problems that need to be solved by the cancer researcher.
The last ten years have seen the publication of a vast amount of data regarding cellular resistance to drugs in cancer cells. Recent studies have demonstrated that drug resistance assays appear to be predictive of clinical response and suggest that clinicians should now be considering the potential applications of these assays in the treatment of patients with hematological neoplasms. This collection of papers from the International Symposium on the Clinical Value of Drug Resistance Assays in Leukemia and Lymphoma, Amsterdam, 1992, provides a state-of-the-art discussion on drug resistance assays and their role in the design and individualization of treatment protocols.
This book analyzes all aspects of metronomic chemotherapy, a new approach involving low-dose, long-term, and frequently administered therapy that has preclinical and clinical activity in various tumors. After an opening section on the pharmacological bases of metronomic chemotherapy, including its antiangiogenic effects and impact on immunity, preclinical studies on various classes of drug are discussed. Clinical applications of metronomic chemotherapy in a wide variety of tumors are then addressed in detail, with description of the results of all published studies. The clinical pharmacology of metronomic chemotherapy is also considered in depth, encompassing pharmacokinetics, pharmacogenetics, pharmacoeconomics, and adverse drug reactions. The book closes by describing the role of this therapy in the veterinarian clinic.
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. - Summarizes the sensitizing role of some tyrosine kinase inhibitors in existing research - Brings recent findings in several cancer types, both experimental and clinically, with a particular emphases on underlying biochemical, genetic, and molecular mechanisms - Provides an updated and comprehensive knowledge regarding the field of combinational cancer treatment
The past decades have seen major developments in the understanding of the cellular and molecular biology of cancer. Significant progress has been achieved regarding long-term survival for the patients of many cancers with the use of tamoxifen for treatment of breast cancer, treatment of chronic myeloid leukaemia with imatinib, and the success of biological drugs. The transition from cytotoxic chemotherapy to targeted cancer drug discovery and development has resulted in an increasing selection of tools available to oncologists. In this Special Issue of Pharmaceuticals, we highlight the opportunities and challenges in the discovery and design of innovative cancer therapies, novel small-molecule cancer drugs and antibody–drug conjugates, with articles covering a variety of anticancer therapies and potential relevant disease states and applications. Significant efforts are being made to develop and improve cancer treatments and to translate basic research findings into clinical use, resulting in improvements in survival rates and quality of life for cancer patients. We demonstrate the possibilities and scope for future research in these areas and also highlight the challenges faced by scientists in the area of anticancer drug development leading to improved targeted treatments and better survival rates for cancer patients.