Death Receptors In Cancer Therapy

An in depth review of our latest understanding of the molecular events that regulate cell death and those molecules that provide targets for developing agonists or antagonists to modulate death signaling for therapeutic purposes. The authors focus on the extrinsic system of death receptors, their regulation and function, and their abnormalities in cancer. Topics of particular interest include resistance to apoptosis, TRAIL signaling, death receptors in embryonic development, mechanisms of caspase activation, and death receptor mutations in cancer. Additional chapters address death signaling in melanoma, synthetic retinoids and death receptors, the role of p53 in death receptor regulation, immune suppression of cancer, and combination therapy with death ligands.

Death receptors play a central role in directing apoptosis in mammalian cells. This process of active cell death is important for a number of biological processes, e.g. for the regulation of the immune system. Death receptors are cell surface receptors that transmit apoptotic signals initiated by corresponding death ligands. Many complex signaling pathways are activated and apoptosis is the final result of a complex biochemical cascade of events. Besides their role in the induction of cell death, evidence now exists that death receptors are able to activate several non-apoptotic signaling pathways which, depending on cellular context, may lead to apoptosis resistance, secretion of pro-inflammatory proteins, proliferation and invasive growth of cancer cells. This book looks at the molecular basis of death receptor signaling and the role of death receptors in cancer development.

Programmed cell death (PCD) plays pivotal roles in tumor progression, cancer therapeutics and resistance of tumor cells to therapy. This book examines the mechanisms involved in mediating and regulating PCD in cancer. It also provides a detailed indication of the utility of PCD in cancer therapy. The book features chapters on the current and future of RNA interference in therapeutics and Pathways involved in Stem Cell Survival and Death.

This volume provides the current understanding of death receptor's/TLR3 signaling regulation in cancer. Death receptors, including TRAIL-R1, TRAIL-R2, Fas and TNF-RI, owing to their ability to trigger apoptosis and to contribute to the elimination of cancer cells by the immune system have been considered, to variable extent, as important therapeutic targets for cancer therapy. But an increasing body of evidence suggests that some of these receptors may also contribute to tumorigenesis, or that new players such as TLR3 may be targeted for cancer therapy due to their ability to behave like death receptors.

Novel drugs are being developed which interact with the programmed cell death (apoptotic) machinery in cancer cells, thereby causing these cells to commit suicide and to be removed from the body. Research is also directed to investigate why the cancer cells sometimes lose the ability to undergo apoptosis after a certain period of time and methods are being developed to reactivate this cell death process. This book is intended for workers in the field and clinicians as a useful guide of the state of affairs in this exciting field which may offer more effective possibilities for treatment of cancer patients. Mels Sluyser is the Editor of the journals APOPTOSIS and ANTI-CANCER DRUGS. He brings together a collection of papers written by the world’s leading experts in these fields.

This book discusses properties of apoptosis and other cell death modalities in cancer pathogenesis and treatment. Its nine chapters discuss modulation of anti-tumor inflammatory and immune responses, effects on the tumor microenvironment, to strategies for improving pro-apoptotic therapies, mechanisms and implications for disease pathogenesis, axl and mer receptor tyrosine kinases, immunogenic apoptotic cell death and anti-cancer immunity and cancer cell death-inducing radiotherapy. This book places the onco-biology of apoptosis in clear and objective perspective through an expertly synthesized series of reviews. Apoptosis in Cancer Pathogenesis and Anti-cancer Therapy is a deft and thorough exploration of cutting-edge research in apoptosis and anti-cancer mechanisms from basic biology to oncology. It highlights a rapidly growing field within cancer research and is essential reading for oncologists, biochemists and advanced graduate students alike.

A key goal in the treatment of cancer is to achieve selective and efficient killing of tumor cells. The aim of Cell Death Signaling in Cancer Biology and Treatment is to describe state-of-the-art approaches and future opportunities for achieving this goal by targeting mechanisms and pathways that regulate cancer cell death. In this book, molecular defects in cell death signaling that characterize cancer cells, including dysregulation of cell death due to overexpression/hyperactivation of oncoproteins, as well as the loss of tumor suppressor proteins will be described. The potential for targeting microRNAs will be discussed. Multiple chapters will describe preclinical and clinical approaches that are currently being used to target epigenetic modifications, DNA repair pathways, and protein chaperones, as a means of provoking tumor cell death. Finally, the development and application of novel agents and approaches for targeting specific components of cell death signaling pathways and machinery will be reviewed.