Expert Reviews in Molecular Medicine

 



Review Article

Telomerase-directed molecular therapeutics


W. Nicol Keith a1c1, Alan Bilsland a1, T.R. Jeffry Evans a1 and Rosalind M. Glasspool a1
a1 Cancer Research UK Department of Medical Oncology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.

Abstract

The management of malignant disease remains one of the most challenging areas of modern medicine. The lifetime risk of developing cancer in the western world is estimated to be as high as 1 in 3. Traditionally, surgery, chemotherapy and radiotherapy have been the primary choice of treatment for patients with malignant tumours. Despite advances in the use and development of conventional cytotoxic agents, the cure rate remains disappointing in most patients with advanced disease of the common solid tumours. Consequently, the development of novel anti-cancer therapies is a high priority in cancer medicine. In recent years, a new generation of cancer therapies has emerged, based on a growing understanding of the molecular events that contribute to malignant transformation. A major difference between normal and cancer cells is the ability of cancer cells to multiply in an unrestricted and ungoverned fashion. In this context, there is considerable interest in elucidating the mechanisms that allow this unrestricted proliferation and that ultimately result in immortal cancer cells. It is now clear that the enzyme telomerase confers immortality on cells in most types of cancer. With the cancer cell reliant on telomerase for its survival, telomerase represents an extremely attractive mechanism-based target for the development of new cancer therapeutics.


Key Words: telomerase; hTERT; hTR; gene therapy; drug development; telomerase inhibition; pharmacodynamics; clinical trials.

Correspondence:
c1 Cancer Research UK Department of Medical Oncology, University of Glasgow, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK. Tel: +44 141 330 4811; Fax: +44 141 330 4127; E-mail: n.keith@beatson.gla.ac.uk