Telomerase Inhibition

This volume presents a compendium of the most recent and advanced methods applied to the rapidly expanding field of telomerase inhibition. The techniques described provide the researcher with a diverse and comprehensive set of tools for the study of telomerase inhibition. The volume is aimed at biochemists, molecular biologists, cancer researchers, and geneticists.

Telomerase, an enzyme that maintains telomeres and endows eukaryotic cells with immortality, was first discovered in tetrahymena in 1985. In 1990s, it was proven that this enzyme also plays a key role in the infinite proliferation of human cancer cells. Now telomere and telomerase are widely accepted as important factors involved in cancer biology, and as promising diagnostic tools and therapeutic targets. Recently, role of telomerase in “cancer stem cells” has become another attractive story. Until now, there are several good books on telomere and telomerase focusing on biology in ciliates, yeasts, and mouse or basic sciences in human, providing basic scientists or students with updated knowledge.

Telomeres are essential functional elements of eukaryotic chromosomes. Their fundamental biological role as protectors of chromosome stability was identified for the first time in the 1930s by Hermann Muller and Barbara McClintock based on pioneering cytological experiments. Modern molecular research carried out more recently revealed that telomeres and telomerase play important roles in processes such as carcinogenesis and cellular senescence. This special issue presents the most recent developments in this highly active field of research. It is becoming increasingly clear that molecular pathways involved in regulation of telomere length and structure are functionally linked with pathways involved in DNA damage response, cellular stress response, chromatin organization and perhaps even pathways that regulate evolutionary chromosome rearrangements. The above functional link is explored by the leading experts in the field of telomere biology. Cell biologists, molecular biologists, oncologists, gerontologists, and radiobiologists with an interest in the role of telomeres/telomerase will appreciate the up-to-date information in this publication.

The fundamental problem that dividing cells have to ov- come is that of end-replication. Chromosomes shorten by many bases during DNA replication and so this presents a major hurdle that a cell has to overcome both to enable it to proliferate and for the larger organism to survive and reproduce. The enzyme telomerase provides a mechanism to ensure chromosome stability in both normal and neoplastic cells. The demonstration of telomerase expression in a majority of tumors and the realization of the potential role of telomerase in aging has opened up the potential for telomerase to be used as a target for therapeutic intervention. There is therefore great interest in the expression and activity of telomerase in a wide range of biological disciplines. Telomeres and Telomerase: Methods and Protocols has been produced as a tool for the many researchers in different areas of cell biology who are interested in following research in the area of telomerase and telomere maintenance, either in the area of fundamental mec- nisms or perhaps in the area of more applied drug discovery work.

This book is a comprehensive and up-to-date review and evaluation of the contemporary status of telomerase research. Chapters in this volume cover the basic structure, mechanisms, and diversity of the essential and regulatory subunits of telomerase. Other topics include telomerase biogenesis, transcriptional and post-translational regulation, off-telomere functions of telomerase and the role of telomerase in cellular senescence, aging and cancer. Its relationship to retrotransposons, a class of mobile genetic elements that shares similarities with telomerase and serves as telomeres in selected organisms, are also reviewed.

Telomere shortening represents one of the basic aspects of ageing and telomere dysfunction could contribute to the accumulation of DNA damage during ageing. This book summarizes evidence and data indicating that telomere dysfunction influences human ageing, diseases and cancer. The book describes our current knowledge on checkpoints that limit cellular lifespan and survival in response to telomere dysfunction. There is special focus on adult stem cells.

Neuroblastoma (NBL) is the most common extracranial solid tumor of childhood, with about 700 new cases of neuroblastoma seen each year in the United States. The 5-year survival rate for children with high-risk NBL is only 50-60%, and this survival rate has not improved over the last 10 years. High-risk patients receive multimodality treatment, including chemotherapy, surgery, radiation therapy, biologic therapy and immunotherapy, all of which are associated with significant morbidity. Recent years have seen many advances in treatment of neuroblastoma, including therapeutic MIBG, immunotherapy, and personalized targeted therapy based on the genetic alterations seen in the tumor. The primary objective of this book is to provide the readers with a comprehensive review of neuroblastoma, from clinical aspects and the currently available treatment to recent advancements and future directions in the field of NBL treatment. The topics and chapters have been compiled keeping in mind a diverse group of readers in different areas of specialty such as pediatric oncology, surgery, radiation oncology, and immunology, as well as physician scientists and basic researchers working in the field of neuroblastoma.