Recent Advances in Anti-Telomerase Cancer Therapy
Pp. 581-631 (51)
Apurva Agrawal, Shweta Dang and Reema Gabrani
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.
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.
Department of Biotechnology, Jaypee Institute of Information Technology, A- 10, Sector- 62, NOIDA- 201307, Uttar Pradesh, India.