Harnessing Telomerase in Cancer Therapeutics

ISSN: 1875-5992 (Online)
ISSN: 1871-5206 (Print)


Volume 16, 12 Issues, 2016


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Anti-Cancer Agents in Medicinal Chemistry

Formerly: Current Medicinal Chemistry - Anti-Cancer Agents

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Editor-in-Chief:
Michelle Prudhomme
Universite Blaise Pascal - C.N.R.S
Aubiere Cedex
France


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Harnessing Telomerase in Cancer Therapeutics



Anti-Cancer Agents in Medicinal Chemistry, 7(4): 475-483.

Author(s): Johans Fakhoury, Graeme A.M. Nimmo and Chantal Autexier.

Affiliation: Bloomfield Centre for Research in Ageing, Lady Davis Institute, Sir Mortimer B. Davis Jewish General Hospital, 3755 Cote-Ste-Catherine Rd., Montreal Quebec, Canada H3T 1E2.

Abstract

Telomerase is an attractive target for anti-cancer therapeutics due to its requirement for cellular immortalization and expression in greater than 85% of human neoplasms. Though initially promising, strategies that inhibit telomerase with either small molecules or antisense oligonucleotides have a major limitation, namely the lag time required for telomere shortening before cellular effects are attained. As alternative approaches, immunotherapy and gene therapy have been tailored to exploit, rather than antagonize telomerase expression and/or activity. Immunotherapy requires the presence of the catalytic subunit of telomerase, hTERT, to elicit an immune response directed towards hTERT peptide-presenting cells. hTERT promoter-driven gene therapy and mutant telomerase RNA (hTR) gene therapy depend on the innate telomerase activity of cancer cells to drive the expression of pro-apoptotic genes and to synthesize mutated DNA sequences onto telomeres, respectively. In addition, we will discuss telomestatin, a G-quadruplex binding ligand that may exert anti-proliferative effects independently of telomere shortening. In this review, the progress, advantages, and limitations of these strategies in the ongoing effort to develop clinically relevant telomerase-based cancer therapeutics will be examined.

Keywords:

Telomerase, immunotherapy, gene therapy, hTERT, hTR, anti-cancer therapy, G-quadruplex, telomestatin.



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Article Details

Volume: 7
Issue Number: 4
First Page: 475
Last Page: 483
Page Count: 9
DOI: 10.2174/187152007781058622
Price: $58
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