Therapies

The growing understanding of the role of telomeres and telomerase in human ageing and cancer biology should ultimately lead to development of novel therapies improving tissue regeneration or impairing cancer growth. The last part of this book summarizes the rationale behind both approaches and shows where the field stands in terms of therapy development. Nicol Keith and Alan E. Bilsland focus on anticancer therapies targeting telomerase or telomere structure. Given that human cancers have very short telomeres and high levels of telomerase compared to non-transformed human tissues, destabilization of telomeres and inhibition of telomerase could both be promising targets in anticancer therapy. It is exciting to see that the first cancer clinical trials have been initiated using a novel telomerase enzyme inhibitor. Somewhat unexpected have been early successes using a telomerase immunotherapy for cancer therapy. In the final chapter Terence Davis and David Kipling introduce therapeutic approaches targeting stress signals downstream of DNA damage and/or telomere dysfunction in Werner syndrome patients; these approaches aim to improve cellular and organismal fitness during ageing. Although they focus on Werner syndrome, it is likely that some of these connections also apply to normal ageing characterized by telomere shortening in various human tissues. In addition, they show that activation of telomerase can prevent the induction of cellular stress responses to some extent, thus representing another therapeutic approach for improving regenerative reserve and organ function in certain premature ageing syndromes and eventually in normal human ageing.

In summary, this book provides a survey of the role of telomeres and telomerase in ageing, diseases, and cancer. The field has made tremendous progress in recent years, and it is becoming ever more clear that telomeres and telomerase have significant influences on human ageing, health, and disease. Telomerase-targeted anticancer therapies are already in human clinical trials, and regenerative therapies are likely to follow soon. It can be anticipated that novel molecular therapies targeting telomeres and telomerase will reach late-stage clinical trials in the near future. This book provides the reader with a fundamental overview of the state of knowledge in basic telomere biology, cellular and organismal ageing, as well as in the emerging field of adult stem cell ageing. Given the progress in translational approaches to target telomeres and telomerase for regenerative and anticancer therapies, this book should be of great interest to students and professionals in both basic science and medicine.

June 2007

Jerry W. Shay K. Lenhard Rudolph

Chapter 1

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