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.

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

Molecular Targeted Radiosensitizers: Opportunities and Challenges provides the reader with a comprehensive review of key pre-clinical research components required to identify effective radiosensitizing drugs. The book features discussions on the mechanisms and markers of clinical radioresistance, pre-clinical screening of targeted radiosensitizers, 3D radiation biology for studying radiosensitizers, in vivo determinations of local tumor control, genetically engineered mouse models for studying radiosensitizers, targeting the DNA damage response for radiosensitization, targeting tumor metabolism to overcome radioresistance, radiosensitizers in the era of immuno-oncology, and more. Additionally, the book features discussions on high-throughput drug screening, predictive biomarkers, pre-clinical tumor models, and the influence of the tumor microenvironment and the immune system, with a specific focus on the challenges radiation oncologists and medical oncologists currently face in testing radiosensitizers in human cancers. Edited by two acclaimed experts in radiation biology and radiosensitizers, with thirteen chapters contributed by experts, this new volume presents an in-depth look at current developments within a rapidly moving field, with a look at where the field will be heading and providing comprehensive insight into the framework of targeted radiosensitzer development. Essential reading for investigators in cancer research and radiation biology.

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. - Presents the most advanced information regarding the role of the autophagic system in life and death - Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both - Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation - Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment - Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available

This, the first of two volumes on personalized medicine in lung cancer, touches on the core issues related to the understanding of lung cancer—statistics and epidemiology of lung cancer—along with the incidence of lung cancer in non-smokers. A major focus of this volume is the state of current therapies against lung cancer—immune, targeted therapies against EGFR TKIs, KRAS, ALK, angiogenesis; the associated challenges, especially resistance mechanisms; and recent progress in targeted drug development based on metal chemistry. Chapters are written by some of the leading experts in the field, who provide a better understanding of lung cancer, the factors that make it lethal, and current research focused on developing personalized treatment plans. With a unique mix of topics, this volume summarizes the current state-of-knowledge on lung cancer and the available therapies.

The present book is an attempt to provide a detailed review of studies that clarify our current understanding of the role of hypoxia in the progression of primary cancer to metastatic disease. It will enable researchers to discover the critical cellular changes that occur under hypoxic conditions and play a role in metastatic dissemination, from the activation of hypoxia-inducible factors, HIF-1 and HIF-2, to the transcriptional profile changes that occur in cancer cells and promote cancer cell survival under detrimental conditions. Readers will discover the methods and challenges involved in imaging and quantifying the degree of hypoxia in a primary tumor. We will provide an understanding of the hypoxia-induced phenotypes that influence heterogeneity, alter the secretome and tumor microenvironment, modify cellular metabolism, and promote immune suppression and resistance to chemotherapy. Finally, we will uncover the therapeutic strategies that are being devised to target the hypoxic microenvironment in the hopes of preventing metastasis and improving the efficacy of standard-of-care cancer treatments. This work is an up to date source of information on the challenges and complexity of the hypoxic tumor microenvironment. Basic and translational scientists, post-doctoral fellows, graduate students, and those interested in how tumors metastasize will find this book a reference that details how hypoxia influences metastatic disease.