Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy

ISSN: 1873-4286 (Online)
ISSN: 1381-6128 (Print)


Volume 20, 42 Issues, 2014


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Oligonucleotides and G-quadruplex Stabilizers: Targeting Telomeres and Telomerase in Cancer Therapy

Author(s): Zachary Crees, Jennifer Girard, Zechary Rios, Gregory M. Botting, Kymberly Harrington, Caleb Shearrow, Luke Wojdyla, Amanda L. Stone, Srijayaprakash B. Uppada, Joseph T. Devito and Neelu Puri

Affiliation: University of Illinois College of Medicine at Rockford, Department of Biomedical Sciences, 1601 Parkview Avenue, Rockford, Illinois 61107.

Abstract

Cancer is a leading cause of death worldwide and an estimated 1 in 4 deaths in the United States is due to cancer. Despite recent advances in cancer treatment, adverse effects related to cancer therapy remain a limiting factor for many patients. The ideal cancer treatment would selectively target cancerous cells while sparing normal, healthy cells to offer maximal therapeutic benefit while minimizing toxicity. Telomeres are structurally unique DNA sequences at the end of human chromosomes, which play an integral role in the cellular mortality of normal cells. As telomeres shorten with successive cellular divisions, cells develop chromosomal instability and undergo either apoptosis or senescence. In many cancers, this apoptosis or senescence is avoided as normal telomere length is maintained by a ribonucleoprotein reverse transcriptase called telomerase. Telomerase is expressed in more than 85% of all cancers and confers cancerous cells with a replicative immortality, which is a hallmark of malignant tumors. In contrast, telomerase activity is not detectable in the majority of normal somatic cell populations. Therefore, the targeting of telomerase and telomere maintenance mechanisms represent a potentially promising therapeutic approach for various types of cancer. This review evaluates the roles of GRN163L, T-oligo and small molecule G-quadruplex stabilizers as potential anticancer therapies by targeting telomerase and other telomere maintenance mechanisms.

Keywords: Clinical trials, G-quadruplex, GRN163L, tankyrase, telomere, telomerase, telomerase inhibitor, T-oligo.

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Article Details

Volume: 20
Issue Number: 41
First Page: 6422
Last Page: 6437
Page Count: 16
DOI: 10.2174/1381612820666140630100702
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