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 . . . . . . . . . . . . . . . . . . . . . . . . . .




Multi-drug Resistance in Cancer


Book Description

With the devastating complication of cancer cells becoming simultaneously resistant to many structurally and mechanistically unrelated drugs, the efficacy of chemotherapeutic management of cancer often becomes severely limited. In Multi-Drug Resistance in Cancer, leading researchers in the field provide 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 protein, to the drug ratio-dependent antagonism and the paradigm of cancer stem cells. The extensive volume also includes strategies to overcome multidrug resistance, from the development of compounds that inhibit drug transporter function to the modulation of transporter expression, as well as techniques for detection and imaging of drug transporters, methods for investigation of drug resistance in animal models, and strategies to evaluate the efficacy of resistance reversal agents. As a volume in the highly successful Methods in Molecular Biology series, this work provides the kind of detailed description and implementation advice that is crucial for getting optimal results. Authoritative and cutting-edge, Multi-Drug Resistance in Cancer offers a state-of-art collection of reviews and methods for both basic and clinician investigators who are interested in the vital study of cancer multi-drug resistance mechanisms and reversal strategies.




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 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.




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.




Breast Cancer Metastasis and Drug Resistance


Book Description

Resistance to therapies, both targeted and systemic, and metastases to distant organs are the underlying causes of breast cancer-associated mortality. The second edition of Breast Cancer Metastasis and Drug Resistance brings together some of the leading experts to comprehensively understand breast cancer: the factors that make it lethal, and current research and clinical progress. This volume covers the following core topics: basic understanding of breast cancer (statistics, epidemiology, racial disparity and heterogeneity), metastasis and drug resistance (bone metastasis, trastuzumab resistance, tamoxifen resistance and novel therapeutic targets, including non-coding RNAs, inflammatory cytokines, cancer stem cells, ubiquitin ligases, tumor microenvironment and signaling pathways such as TRAIL, JAK-STAT and mTOR) and recent developments in the field (epigenetic regulation, microRNAs-mediated regulation, novel therapies and the clinically relevant 3D models). Experts also discuss the advances in laboratory research along with their translational and clinical implications with an overarching goal to improve the diagnosis and prognosis, particularly that of breast cancer patients with advanced disease.




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




Central Nervous System Metastases


Book Description

This book provides a comprehensive overview of brain metastases, from the molecular biology aspects to therapeutic management and perspectives. Due to the increasing incidence of these tumors and the urgent need to effectively control brain metastatic diseases in these patients, new therapeutic strategies have emerged in recent years. The volume discusses all these innovative approaches combined with new surgical techniques (fluorescence, functional mapping, integrated navigation), novel radiation therapy techniques (stereotactic radiosurgery) and new systemic treatment approaches such as targeted- and immunotherapy. These combination strategies represent a new therapeutic model in brain metastatic patients in which each medical practitioner (neurosurgeon, neurologist, medical oncologist, radiation oncologist) plays a pivotal role in defining the optimal treatment in a multidisciplinary approach. Written by recognized experts in the field, this book is a valuable tool for neurosurgeons, neuro-oncologists, neuroradiologists, medical oncologists, radiation oncologists, cognitive therapists, basic scientists and students working in the area of brain tumors.




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.




Chemosensitivity


Book Description

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.