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