Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance


Book Description

Biological Mechanisms and the Advancing Approaches to Overcoming Cancer Drug Resistance, Volume 12, discusses new approaches that are being undertaken to counteract tumor plasticity, understand and tackle the interactions with the microenvironment, and disrupt the rewiring of malignant cells or bypass biological mechanism of resistance by using targeted radionuclide therapies. This book provides a unique opportunity to the reader to understand the fundamental causes of drug resistance and how different approaches are applied. It is a one-stop-shop to understand why it is so difficult to treat cancer, and why only a very few patients respond to therapy and a significant portion develop resistance. Despite a rapid development of more effective anti-cancer drugs and combination therapies, cancer remains the leading cause of lethality in the developed world. The main reason for this is the ability of heterogeneous subpopulations of tumor cells interacting with constantly evolving tumor microenvironment to resist elimination and eventually, trigger cancer relapse. In this book, experts review current concepts explaining molecular and biological mechanisms of cancer drug resistance and discussing advancing approaches for overcoming these therapeutic challenges. Provides the most updated knowledge on the mechanisms of cancer drug resistance and the emerging therapeutic approaches reviewed by experts in the field Brings detailed analyses of most important recently reported developments related to drug resistance and their relevance to overcoming it in cancer patients Discusses in-depth molecular mechanisms and novel concepts of cancer resistance to conventional and advanced therapies




Cancer Drug Resistance


Book Description

Leading experts summarize and synthesize the latest discoveries concerning the changes that occur in tumor cells as they develop resistance to anticancer drugs, and suggest new approaches to preventing and overcoming it. The authors review physiological resistance based upon tumor architecture, cellular resistance based on drug transport, epigenetic changes that neutralize or bypass drug cytotoxicity, and genetic changes that alter drug target molecules by decreasing or eliminating drug binding and efficacy. Highlights include new insights into resistance to antiangiogenic therapies, oncogenes and tumor suppressor genes in therapeutic resistance, cancer stem cells, and the development of more effective therapies. There are also new findings on tumor immune escape mechanisms, gene amplification in drug resistance, the molecular determinants of multidrug resistance, and resistance to taxanes and Herceptin.




Molecular Mechanisms of Tumor Cell Resistance to Chemotherapy


Book Description

​​​​​This volume gives the latest developments in on the mechanisms of cancer cell resistance to apoptotic stimuli, which eventually result in cancer progression and metastasis. One of the main challenges in cancer research is to develop new therapies to combat resistant tumors. The development of new effective therapies will be dependent on delineating the biochemical, molecular, and genetic mechanisms that regulate tumor cell resistance to cytotoxic drug-induced apoptosis. These mechanisms should reveal gene products that directly regulate resistance in order to develop new drugs that target these resistance factors and such new drugs may either be selective or common to various cancers. If successful, new drugs may not be toxic and may be used effectively in combination with subtoxic conventional drugs to achieve synergy and to reverse tumor cell resistance. The research developments presented in this book can be translated to produce better clinical responses to resistant tumors.




Drug Resistance in Cancer


Book Description

Drug resistance in cancer, whereby a portion of cancer cells evades chemotherapy, poses a profound and continuing challenge for the effective treatment of cancer. The principles underlying the biological mechanisms behind this phenomenon are clearly explained in this volume. A deeper understanding of drug resistance requires a quantitative appreciation of the dynamic forces that shape tumor growth, including spontaneous mutation and selection processes. The authors seek to explain and to simplify these complex mechanisms, and to place them in a clinical context. Clearly explained mathematical models are used to illustrate the biological principles and provide an insight into tumor development and the effectiveness and limitations of drug treatment. The volume is suitable for those with a nonmathematical background and aims to enhance the effectiveness of cancer therapy. This is the first book to provide such an integrated account, in a form accessible to both doctor and scientist.







Cancer Drug Resistance


Book Description

This volume discusses the latest techniques used to identify cancer drug resistance determinants at the molecular, cellular, and functional levels. Chapters in this book cover up-to-date topics including tumor-microenvironment cell co-culture methods and microfluidics systems; workflows for functional assessment of drug resistance in vitro and in vivo; quantitative techniques for identifying quiescent blood-flow circulating cells; and single-cell characterization methods, such as mass cytometry. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Cancer Drug Resistance: Methods and Protocols is a valuable resource for all scientists and researchers who are looking to learn more about the latest developments in understanding and overcoming anticancer drug resistance.




Cytotoxic Drug Resistance Mechanisms


Book Description

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.




Molecular and Clinical Advances in Anticancer Drug Resistance


Book Description

The importance of drug resistance in cancer chemotherapy cannot be over stated. The 500,000 patients who die every year from cancer in the United States have, in most cases, been treated with chemotherapy. Many of these patients responded initially to chemotherapy, but death resulted from the development of drug-resistant tumors. In the first volume in the series. Drug Resistance in Chemotherapy the results of comprehensive laboratory studies aimed at understanding the mechanisms for resistance to individual agents and to the development of broad cross-resistance were described. In the past 2 years there has been substantial progress in understanding the molecular biology associated with these mechanisms of drug resistance. For the first time we are starting to understand which mechanisms are playing an im portant role in human tumors, and even more importantly, clinical trials have recently been initiated in an effort to reverse specific forms of drug resistance. The purpose of this volume is to describe the new advances, both at the molecular level and in the clinic regarding mechanisms of drug resistance and potential ways this resistance can be circumvented. This volume is focused upon mechanisms of resistance associated with two major classes of anticancer drugs: alkylating agents (including cisplatin) and the natural products (e. g. , adriamycin and vinblastine). The first section of the book describes new insights into the genetic mechanisms associated with drug resistance.




Mechanisms of Drug Resistance in Cancer Therapy


Book Description

A major objective of this book is to reveal unprecedented opportunities to understand and overcome drug resistance through the clinical assessment of rational therapeutic drug combinations and the use of predictive and prognostic biomarkers to enable patient stratification and tailor treatments. It offers to the readers an updated overview on the possible reasons of failure of new and promising therapeutic opportunities.




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