Beyond Apoptosis: Cellular Outcomes of Cancer Therapy PDF

Preface

BEYOND APOPTOSIS

Over the past decade, much of the effort in understanding how chemotherapy or radiation therapy stops tumor growth has been concentrated on apoptosis, a physiological program of cell death. Although the existing anticancer agents are capable of inducing apoptosis in tumor cells, the accumulating body of evidence indicates that apoptosis plays only a limited role in determining the success of cancer therapy. In recent years, this realization prompted the examination of alternative mechanisms of the antiproliferative action of anticancer agents. These alternative mechanisms include non-apoptotic forms of cell death, terminal cell cycle arrest through the program of cell senescence, and the process of mitotic catastrophe, a general term that designates different forms of abnormal mitosis that lead to eventual cell death or cessation of cell division. Some of these nonapoptotic responses have been already shown to be significant players in stopping the growth of tumor cells, while some other responses (in particular non-apoptotic forms of programmed cell death) have not yet been sufficiently investigated in the setting of cancer therapy. The goal of this book is to examine the relative contribution of apoptosis to cancer treatment response and to acquaint the readers with new concepts in non-apoptotic cell death, senescence, and mitotic catastrophe.

Toward this goal, the first section of the book will include a general overview of apoptosis and critical reviews of its role in the toxicity of anticancer agents to both tumor cells and normal tissues. The second section will provide a description of different non-apoptotic forms of cell death (such as necrosis, paraptosis, autophagic cell death, and others) that were defined primarily in noncancer context. The third section will deal with the relevance and mechanisms of treatment-induced senescence in tumor and normal cells and with both tumorsuppressing and tumor-promoting effects of senescent cells on their environment.

The fourth section will address the forms and consequences of mitotic catastrophe as a critical event preceding tumor cell death or senescence, as well as other factors that determine different forms of cell death or senescence in tumor cells treated with anticancer agents. To help the readers understand the morphological and kinetic differences between different forms of cell death, senescence, or mitotic catastrophe, the book will include not only the necessary morphological illustrations but also a DVD containing additional color images and video clips from time-lapse microscopic studies of different forms of cell death and mitotic catastrophe.