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DNA G-Quadruplexes, Telomere-Specific Proteins and Telomere-Associated Enzymes as Potential Targets for New Anticancer Drugs

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Abstract

Telomeres and telomerase have been subjects to a tremendousattention from scientists and oncologists during the past 5 years.This interest has been motivated by the potential of telomerase asa tumor marker for the diagnosis and the prognosis of cancer.The possible use of telomerase or telomeres as new targets foranticancer drugs also triggered investigations. The expression of telomerasewas found in overall 85% of cancers. Telomerase is early expressedduring oncogenesis with a gradient indicating that a high level oftelomerase expression could be associated with a bad prognosis.Therefore, drugs targeting telomerase and telorneres might beuseful in many human tumors with little restrictions regarding thetumor type or on the stage of the disease. Moreover, sincetelomerase is not or slightly expressed in normal cells, it hasbeen postulated that drugs targeting telomerase would induce lowtoxicity.

The race for the discovery of telomerase inhibitors has startedwhile the identification of the components controlling telomerase,telomeres, cell survival, senescence, and apoptosis was still inprogress. The recent identification of components regulatingtelomere length and telomerase expression (TRF1, TRF2, andtankyrase) opened a variety of new opportunities to controltelomerase/telomere interactions. Meanwhile, a proof of principlewas provided that changing telomere interactions with telomere binding proteins by chemical or biological means can induce cancercell death. Interestingly, recent data challenge the old paradigm whichsuggested that a long exposure to telomerase and telomereinhibitors is necessary to induce anticancer effects.

In this paper, we review the most recent information concerning theregulation of telomere length and telomerase expression, withemphasis on mechanisms that might translate into new drugdiscovery.

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Authors and Affiliations

  1. Department of Medicine, Institute Gustave-Roussy, Villejuif, France

    Eric Raymond & Jean-Charles Soria

  2. Telomerase Working Group, Institute for Drug Development, San Antonio, TX, USA

    Jean-Charles Soria, Elzbieta lzbicka, Laurence Hurley & Daniel D. Von Hoff

  3. Laboratoire de Radiopathologie, DRR, DSV, CEA, Fontenay aux Roses, France

    Francois Boussin

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  1. Eric Raymond
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  5. Laurence Hurley
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Raymond, E., Soria, JC., lzbicka, E. et al. DNA G-Quadruplexes, Telomere-Specific Proteins and Telomere-Associated Enzymes as Potential Targets for New Anticancer Drugs. Invest New Drugs 18, 123–137 (2000). https://doi.org/10.1023/A:1006373812586

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