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      Targeted Inhibition of Telomerase in Human Cancer: Will It Be a Double-Edged Sword?

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      , ,
      Oncology Research and Treatment
      S. Karger AG

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          Abstract

          More than 80% of human malignancies express telomerase activity, while normal somatic tissues in general lack it. During each normal cell division, there is a constant loss of DNA sequences at chromosomal ends, which is due to the ‘end-replication problem’ of conventional DNA polymerase. Critical shortening of telomeres induces cell cycle arrest and eventually cell death. Telomerase, a ribonucleoprotein complex with a RNA (TR) and a catalytic subunit (TERT) as core components, is able to add reitineratedly telomeric repeat sequences to the very ends of chromosomes. It was suggested that activation of telomerase in tumor cells has a major impact on their continuous growth. Indeed, transfection of TERT constructs into various normal human cell types led to telomere elongation or stabilization and, most importantly, cellular immortalization. Conversely, inhibition of telomerase in tumor cell lines induced growth arrest, at least in first experimental settings. Such initial success implies that drug-mediated abrogation of telomerase action might be an ideal adjuvant treatment for cancer patients. There are, however, legitimate concerns about the generalization of such an approach.

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          Author and article information

          Journal
          ONK
          Oncol Res Treat
          10.1159/issn.2296-5270
          Oncology Research and Treatment
          S. Karger AG
          2296-5270
          2296-5262
          2001
          February 2001
          02 March 2001
          : 24
          : 1
          : 22-26
          Affiliations
          Institut für Tumorbiologie-Krebsforschung, Universität Wien
          Article
          50277 Onkologie 2001;24:22–26
          10.1159/000050277
          11441276
          6b925a34-d378-42e6-b012-ce5da9e746bd
          © 2001 S. Karger GmbH, Freiburg

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          History
          Page count
          Pages: 5
          Categories
          Review Article · Übersichtsarbeit

          Oncology & Radiotherapy,Pathology,Surgery,Obstetrics & Gynecology,Pharmacology & Pharmaceutical medicine,Hematology

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