Recent Advances in Anti-Telomerase Cancer Therapy

Telomerase, a specialised RNA-directed DNA polymerase extends and stabilises the telomeres at the ends of the eukaryotic chromosomes. The progressive loss of telomeres results in limited number of cell divisions and has been linked to the mechanism of human cellular ageing. Tumor cells marked by indefinite proliferation have stable telomere length maintained by telomerase. The differential expression of the telomerase enzyme in normal and cancer cells has led to the evolution of tumor specific anti-telomerase approaches which inhibit the telomerase enzyme activity so as to destabilise and shorten the telomeres leading to senescence in cancer cells.

In the current chapter, we have selected nine tumor specific anti-telomerase approaches based on their mechanism of action or the target components of the human telomerase enzyme: Antisense-oligonucleotides, hammerhead ribozymes, dominant negative human telomerase reverse transcriptase (DN- hTERT), reverse-transcriptase inhibitors, immunotherapy, G-quadruplex stabilisers, gene therapy, small molecule inhibitors and RNA interference. Recent research developments for each of the anti-telomerase approaches with the detailed analysis of specific granted patents from the perspective of different claims and downstream applications have been provided. A comprehensive list of patents for the different anti-telomerase approaches which includes information regarding the authors and institutional ownership along with the year of issue of the patent has also been provided. The chapter also presents a perspective on nanotechnology based delivery of anti- telomerase cancer therapeutics.

Keywords: Antisense-oligonucleotides (AS-ODN), anti-telomerase, apoptosis, dominant negative human telomerase reverse transcriptase (DN- hTERT), G-quadruplex stabilisers, gene-directed enzyme pro-drug therapy (GDEPT), gene therapy, hammerhead ribozymes, immunotherapy, nanoparticles, nanotechnology, patents, reverse transcriptase inhibitors, RNA interference, small molecule inhibitors, telomerase, telomeres, tumor, tumor associated antigen (TAA), vaccines.