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37 - Telomerase: target for cancer treatment

from Part 2.4 - Molecular pathways underlying carcinogenesis: DNA repair

Published online by Cambridge University Press:  05 February 2015

By
Jerry W. Shay  and
Woodring E. Wright
Edited by
Edward P. Gelmann ,
Charles L. Sawyers  and
Frank J. Rauscher, III
Jerry W. Shay
Affiliation:
University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, TX, USA
Woodring E. Wright
Affiliation:
University of Texas Southwestern Medical Center, Department of Cell Biology, Dallas, TX, USA
Edward P. Gelmann
Affiliation:
Columbia University, New York
Charles L. Sawyers
Affiliation:
Memorial Sloan-Kettering Cancer Center, New York
Frank J. Rauscher, III
Affiliation:
The Wistar Institute Cancer Centre, Philadelphia
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Summary

Introduction

Telomerase, a cellular reverse transcriptase that adds DNA to the ends of chromosomes, is reactivated or up-regulated in the vast majority of human advanced malignancies, and is thus an almost universal target for human cancer. Most human tumors not only express telomerase, but also have very short telomeres, whereas telomerase activity is absent or at lower levels in normal tissues, which also have longer telomeres. This relationship between activation of telomerase activity and short telomeres in human malignancies makes the inhibition of telomerase a novel target for cancer therapeutics. Importantly, the mode of action of telomerase inhibitors predicts minimal side effects on normal stem cells that can express telomerase. Here we summarize the role of telomeres and telomerase in cancer and review the current status of ongoing telomerase clinical trials. This chapter will also discuss the relationship of telomerase to cancer stem cells. Central questions remaining include: What are the key safety concerns, such as the effect of telomerase inhibitors on normal stem cells that express some telomerase? Do cancer stem cells express telomerase activity? What effect will telomerase inhibitors have if cancer stem cells are more quiescent than the bulk of the more differentiated tumor cells? Will human cancers become resistant to telomerase inhibitors?

Type
Chapter
Information
Molecular Oncology
Causes of Cancer and Targets for Treatment
 , pp. 442 - 451
Publisher: Cambridge University Press
Print publication year: 2013

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