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Targeting telomerase for cancer therapy

Oncogene volume 39, pages 5811–5824 (2020)Cite this article

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Abstract

Telomere maintenance via telomerase reactivation is a nearly universal hallmark of cancer cells which enables replicative immortality. In contrast, telomerase activity is silenced in most adult somatic cells. Thus, telomerase represents an attractive target for highly selective cancer therapeutics. However, development of telomerase inhibitors has been challenging and thus far there are no clinically approved strategies exploiting this cancer target. The discovery of prevalent mutations in the TERT promoter region in many cancers and recent advances in telomerase biology has led to a renewed interest in targeting this enzyme. Here we discuss recent efforts targeting telomerase, including immunotherapies and direct telomerase inhibitors, as well as emerging approaches such as targeting TERT gene expression driven by TERT promoter mutations. We also address some of the challenges to telomerase-directed therapies including potential therapeutic resistance and considerations for future therapeutic applications and translation into the clinical setting. Although much work remains to be done, effective strategies targeting telomerase will have a transformative impact for cancer therapy and the prospect of clinically effective drugs is boosted by recent advances in structural models of human telomerase.

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Fig. 1: Therapeutic strategies for targeting telomerase.
Fig. 2: TERT promoter regulation: a new therapeutic avenue in cancer?.

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Acknowledgements

Work in our laboratory is supported by NIH grants R01CA215733, R01CA226888, P01CA114046, P50CA174523, P30CA010815, the Department of Defense Melanoma Research Program (W81XWH-20-1-0356), the PA Department of Health and Martha W. Rogers Trust.

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  1. Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, PA, USA

    Adam N. Guterres & Jessie Villanueva

  2. Melanoma Research Center, The Wistar Institute, Philadelphia, PA, USA

    Jessie Villanueva

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  1. Adam N. Guterres
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Correspondence to Jessie Villanueva.

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Guterres, A.N., Villanueva, J. Targeting telomerase for cancer therapy. Oncogene 39, 5811–5824 (2020). https://doi.org/10.1038/s41388-020-01405-w

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