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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 . . . . . . . . . . . . . . . . . . . . . . . . . .
Amazing anticancer therapy advancements have been made in the last decade due to tremendous innovations. Nonetheless, drug resistance remains a major challenge that limits the effectiveness of anticancer therapies, causing cancer recurrence and metastasis and being a major cause of cancer-related death. Drug resistance can be caused by complex molecular mechanisms such as gene mutations, epigenetic dysregulation, microenvironment alterations, etc. Many clinical strategies, including combination therapies and epigenetic drugs, have been used to avoid or reverse drug resistance effectively. However, the progression of cancers (in patients under treatment) or the lack of response of cancer patients indicate that current approaches to overcome resistance are far from sufficient, and more work is needed.
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 is a printed edition of the Special Issue "Natural Products for Cancer Prevention and Therapy" that was published in Nutrients
Despite the significant advances in cancer therapy made through constant evaluation and analysis of treatment aftereffects, the disease still remains one of the foremost causes of mortality worldwide killing more than 12 million people annually. The prime reason behind the failure of conventional chemotherapeutics which are used as the chief regimen in the comprehensive treatment of cancers is the development of chemoresistance. It can be either intrinsic or acquired and is primarily mediated via different key regulators like MDR, MAPK, NF-κB, PI3K/Akt, Wnt signaling pathways etc. Thus, agents which can target these regulatory elements or pathways and in turn sensitize cancer cells to chemotherapy holds immense prospect. However, there is barely such comprehensive work available in scientific literature that explains how chemosensitization of cancer cells functions using different drug combinations and exhibit synergism. This book provides a detailed description of chemoresistance and chemosensitization, targets for chemosensitization and various approaches adapted in the process of chemosensitization. Furthermore, the book explicates the role of various chemosensitizers, both natural and synthetic in sensitizing cancer cells and also details the current research findings on chemosensitization of different cancer types in both pre-clinical and clinical settings.
Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.
This book provides the first comprehensive overview of a new scientific discipline termed Geroscience. Geroscience examines the molecular and cellular mechanisms that might explain why aging is the main risk factor for most chronic diseases affecting the elderly population. Over the past few decades, researchers have made impressive progress in understanding the genetics, biology and physiology of aging. This book presents vital research that can help readers to better understand how aging is a critical malleable risk factor in most chronic diseases, which, in turn, could lead to interventions that can help increase a healthy lifespan, or ‘healthspan.’ The book begins with an analysis of the Geroscience hypothesis, as well as the epidemiological underpinnings that define aging as a candidate main risk factor for most chronic diseases. Next, each chapter focuses on one particular disease, or group of diseases, with an emphasis on how basic molecular and cellular biology might explain why aging is a major risk factor for it. Coverage in the book includes: cancer, cardiovascular disease, dementias, stroke, Parkinson's and Alzheimer’s diseases, osteoporosis, arthritis, diabetes asthma, emphysema, kidney disease, vision impairment, and AIDS/HIV. It finishes with a chapter on pain in the elderly and an overview of future steps needed to bring the newly acquired knowledge into the clinic and the public at large.
Cancer is the second leading cause of death among adults in the United States after heart disease. However, improvements in cancer treatment and earlier detection are leading to growing numbers of cancer survivors. As the number of cancer survivors grows, there is increased interest in how cancer and its treatments may affect a person's ability to work, whether the person has maintained employment throughout the treatment or is returning to work at a previous, current, or new place of employment. Cancer-related impairments and resulting functional limitations may or may not lead to disability as defined by the U.S. Social Security Administration (SSA), however, adults surviving cancer who are unable to work because of cancer-related impairments and functional limitations may apply for disability benefits from SSA. At the request of SSA, Diagnosing and Treating Adult Cancers and Associated Impairments provides background information on breast cancer, lung cancer, and selected other cancers to assist SSA in its review of the listing of impairments for disability assessments. This report addresses several specific topics, including determining the latest standards of care as well as new technologies for understanding disease processes, treatment modalities, and the effect of cancer on a person's health and functioning, in order to inform SSA's evaluation of disability claims for adults with cancer.
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. - Provides comprehensive, core knowledge related to the entire discipline of glioblastoma chemoresistance, from its many etiological mechanisms, to specific strategies to reverse resistance - Presents current information from an international team of experts on the basic science, pre-clinical research, and clinical management of glioblastoma chemoresistance - Discusses molecular and cellular mechanisms behind therapy resistant glioblastoma cells, as well as the therapeutic strategies available to counter this resistance