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Drug Insight: cancer cell immortality—telomerase as a target for novel cancer gene therapies

Nature Clinical Practice Oncology volume 1, pages 88–96 (2004)Cite this article

Abstract

Rapid advances in our understanding of the molecular basis of cancer development and progression over the past three decades have led to the design of new potential cancer therapies. High throughput target validation and expression studies are expected to yield a powerful arsenal of new cancer treatments, but untangling the complex pathways underlying the major cancer phenotypes remains a significant challenge. A considerable body of evidence in recent years implicates deregulated expression of a single multi-component enzyme, telomerase, as a causative factor at the heart of immortalization in the vast majority of human tumors. This review highlights the potential of telomerase as a target for novel cancer therapies. The potential of exploiting the selectivity of the telomerase family of genes within cancer cells to develop gene therapy strategies is discussed, and the progress towards translating these novel therapeutics from the laboratory to the clinic is reviewed.

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Figure 1: The products of two genes are required to reconstitute basic telomerase activity; the RNA component, hTR, which includes the template for synthesis of telomere DNA, and the protein catalytic component, hTERT, which has reverse transcriptase activity.
Figure 2: Telomerase-directed molecular therapeutics.
Figure 3: (A) Telomerase-directed gene therapy.

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Acknowledgements

Research in the author's laboratory is supported by Cancer Research UK, and Glasgow University.

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Authors and Affiliations

  1. Molecular Oncology and Head of the Telomerase Therapeutics Program at the CRUK Centre for Oncology and Applied Pharmacology, Glasgow

    W Nicol Keith, Alan Bilsland, Maryon Hardie & TR Jeffry Evans

  2. Centre for Oncology and Applied Pharmacology, University of Glasgow,

    W Nicol Keith, Alan Bilsland, Maryon Hardie & TR Jeffry Evans

  3. Medical Oncology at the Beatson Oncology Centre, Glasgow

    W Nicol Keith, Alan Bilsland, Maryon Hardie & TR Jeffry Evans

  4. Medical Oncology at the Centre for Oncology and Applied Pharmacology, University of Glasgow and Honorary Consultant in Medical Oncology at the Beatson Oncology Centre, Glasgow

    W Nicol Keith, Alan Bilsland, Maryon Hardie & TR Jeffry Evans

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Correspondence to W Nicol Keith.

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BYSTANDER EFFECT

Tumor regression when a fraction of the tumor mass is genetically modified

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Keith, W., Bilsland, A., Hardie, M. et al. Drug Insight: cancer cell immortality—telomerase as a target for novel cancer gene therapies. Nat Rev Clin Oncol 1, 88–96 (2004). https://doi.org/10.1038/ncponc0044

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