• Open Access

Targeting the telomere and shelterin complex for cancer therapy: current views and future perspectives

Authors


Correspondence to: Professor W. Nicol KEITH,
University of Glasgow, Institute of Cancer Sciences, Beatson Laboratories,
Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK.
Tel.: 0044 141 330 4811
Fax: 0044 141 330 4127
E-mail: nicol.keith@glasgow.ac.uk

Abstract

  • • Introduction
  • • Targeting the telomere
  • • Composition of the shelterin complex
  • • Shelterin targeting
    approaches
  • • Conclusion

Aberrant telomere homeostasis is essential for cell immortality, enabling cells to evade telomere dependent senescence. Disruption of telomere structure and function in cancer cells is highly toxic as shown by detailed pre-clinical evaluation of telomerase inhibitors. Under telomerase inhibition, cells must divide sufficiently frequently to allow one or more telomeres to shorten to an unprotected length. Functioning telomeres are disguised from the DNA damage machinery by DNA remodelling and other activities of the telomere binding complex shelterin. Direct interference with shelterin has been shown to result in cell killing and small molecules directly targeting telomere DNA also have anti-tumour effects partially dependent on shelterin disruption. However, shelterin components have not generally been regarded as therapeutic targets in their own right. In this review, we explore the possibilities for therapeutic targeting of the shelterin complex.

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