Multi-Drug Resistance in Cancer


Book Description

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 Efflux Pumps in Cancer Resistance Pathways: From Molecular Recognition and Characterization to Possible Inhibition Strategies in Chemotherapy


Book Description

Drug Efflux Pumps in Cancer Resistance Pathways: From Molecular Recognition and Characterization to Possible Inhibition Strategies in Chemotherapy, Volume Seven, describes the fundamental aspects of efflux pumps of the ATP-binding cassette superfamily in cancer resistance pathways, along with strategies to target and improve chemotherapy efficacy. Pumps of the ATP-binding cassette superfamily (ABCs) regulate the access of drugs to the intracellular space. In this context, the overexpression of ABCs is a well-known mechanism of multidrug resistance in cancer and is associated with therapeutic failure. Cancer types discussed include breast, endocrine, hematologic, gastrointestinal, musculoskeletal, lung, skin and central nervous system cancers. The book is a valuable source for researchers and advanced students in cancer, biology, pharmacology, pharmaceutical sciences, biomaterials and medical/clinical sciences that are interested in accessing a comprehensive compendium on efflux pumps in mechanisms of cancer resistance. Offers comprehensive and detailed descriptions of the basic aspects of efflux pumps in a very schematic and didactic manner Describes the involvement of efflux pumps in cancer resistance in different cancer types Encompasses an updated overview on state-of-the-art approaches that capitalize on their inhibition to improve chemotherapy and overcome resistance




Clinically Relevant Resistance in Cancer Chemotherapy


Book Description

Over the last several decades, the introduction of new chemotherapeutic drugs and drug combinations has resulted in increased long term remission rates in several important tumor types. These include childhood leukemia, adult leukemias and lymphomas, as well as testicular and trophoblastic tumors. The addition of high-dose chemotherapy with growth factor and hemopoietic stem cell support has increased clinical remission rates even further. For the majority of patients with some of the more common malignancies, however, palliation (rather than cure) is still the most realistic goal of chemotherapy for metastatic disease. The failure of chemotherapy to cure metastatic cancer is commonly referred to among clinicians as "drug resistance". This phenomenon can, however, often be viewed as the survival of malignant cells that resulted from a failure to deliver an effective drug dose to the (cellular) target because of anyone of or combination of a multitude of individual factors. Clinically, this treatment failure is often viewed as the rapid occurrence of resistance at the single cell level. However, in experimental systems, stable drug resistance is usually relatively slow to emerge.




Drug Resistance in Leukemia &


Book Description

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.




Drug Transporters


Book Description

It is increasingly recognized that various transporter proteins are expressed throughout the body and determine absorption, tissue distribution, biliary and renal elimination of endogenous compounds and drugs and drug effects. This book will give an overview on the transporter families which are most important for drug therapy. Most chapters will focus on one transporter family highlighting tissue expression, substrates, inhibitors, knock-out mouse models and clinical studies.




Chemosensitivity Testing in Oncology


Book Description

Over the past 50 years many in vitro and in vivo drug response assay systems have been developed to determine the potential - tivity of chemotherapy agents. The idea was to eliminate ineffective agents and unnecessary toxic treatment while selecting drugs active in vitro or in the mouse model that might increase the probability of response in the patient. None of these test models, however, achieved routine clinical application in the past. This might be at least in part - lated to large discrepancies that were described between the s- cess rate of the assay systems and the clinical benefit in cancer - tients. The heterogeneity of chemosensitivity that exists between different tumors as well as between individual tumor lesions may be one explanation for these findings. Furthermore, different assay end points such as proliferation, metabolism, and vitality were - veloped to evaluate the effects of cytostatic drugs on tumor cells, and these might be related to the differing results. However, knowledge about procedures for assay-assisted treatment selection has increased rapidly within the past few years, and several studies suggest that test-directed chemotherapy selection now may - prove response rates and survival in various types of tumors. The International Society for Chemosensitivity Testing in - cology (ISCO) was founded to promote, coordinate, and improve clinical and laboratory research in the field of predictive drug te- ing in human tumor cells.




Protein Kinase Inhibitors as Sensitizing Agents for Chemotherapy


Book Description

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




Reversal of Multidrug Resistance in Cancer


Book Description

This critical, state-of-the-art review brings together the scattered and often controversial information on multidrug resistance reversal. Leading scientists in the field cover P-glycoprotein, the genetics of resistance, and its reversal by drugs. Resistance modifiers and modulators are tabulated and critically evaluated. Reversal of Multidrug Resistance in Cancer is important reading for oncologists, cancer chemotherapists, and other cancer researchers.




Drug Transporters in Drug Disposition, Effects and Toxicity


Book Description

This book provides with a comprehensive overview of the role of drug transporters in drug disposition and efficacy/toxicity, as well as drug-drug interactions and recent advances in the field. Transporters are known determinants of drug disposition and efficacy/toxicity. In general, they are divided into solute carrier (SLC) and ATP binding cassette (ABC) families, and are located along cell membranes, where they mediate drug uptake into cells and export out of cells. Drug transporters are essential in maintaining cell homeostasis, and their gene mutations may cause or contribute to severe human genetic disorders, such as cystic fibrosis, neurological disease, retinal degeneration, anemia, and cholesterol and bile transport defects. Conversely, some diseases may also alter transporter functions and expressions, in turn aggravating disease process. Further, since over-expression of some ABC transporters is a potential contributor to multidrug-resistance (MDR), the book presents a number of strategies to overcome MDR, including ABC transporter inhibitors and applying epigenetic methods to modulate transporter expressions and functions. This book is useful for graduate students and professionals who are looking to refresh or expand their knowledge of this exciting field.




Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies


Book Description

Osteosarcoma in Adolescents and Young Adults: New Developments and Controversies is the fifth volume in the series `Cancer Treatment, and Research' devoted to pediatric oncology. Like its immediate predecessor, Hodgkin's Disease in Children: Controversies and Current Practice, this volume also deals with the current state of affairs: where do researchers differ in opinions or firmly held beliefs? What does the future hold for research or for the patients who have benefited from research and are now cured? etc. The first part deals with preclinical and clinical issues that relate to the disease and the second part deals with the results of recent trials and in some cases ongoing trials. It could be argued that section B Pharmacology, Section D Radiotherapy and Section E Surgery of part one belong to part two; however in these sections we have tried to focus on one discipline and in part two, we have tried to focus on the results of multidisciplinary trials. A third part includes a few critiques and editorial comments. This volume was prepared and planned for both basic and clinical oncologists. It is hoped that the basic scientists will gain some insight into the problems of their clinical colleagues and that the clinicians will be willing to read to the more basic articles. It is not a text for students (or for that matter physicians) who want all things to be laid out in `black and white'. But it is a text for those students who want to know how vibrant this field of research is and are willing to stand in awe of how much research needs to be done.