Title:Telomerase as a Cancer Target. Development of New Molecules
Volume: 16
Issue: 22
Author(s): D.L. Mengual Gomez, R.G. Armando, C.S. Cerrudo, P.D. Ghiringhelli and D.E. Gomez
Affiliation:
Keywords:
Telomere, Telomerase, Inhibitor, Cancer, Preclinical, Clinical trials.
Abstract: Telomeres are the terminal part of the chromosome containing a long repetitive and noncodifying
sequence that has as function protecting the chromosomes. In normal cells, telomeres lost
part of such repetitive sequence in each mitosis, until telomeres reach a critical point, triggering at that
time senescence and cell death. However, in most of tumor cells in each cell division a part of the telomere
is lost, however the appearance of an enzyme called telomerase synthetize the segment that just
has been lost, therefore conferring to tumor cells the immortality hallmark. Telomerase is significantly
overexpressed in 80–95% of all malignant tumors, being present at low levels in few normal cells, mostly stem cells. Due
to these characteristics, telomerase has become an attractive target for new and more effective anticancer agents. The capability of inhibiting telomerase in tumor cells should lead to telomere shortening, senescence and apoptosis. In this work,
we analyze the different strategies for telomerase inhibition, either in development, preclinical or clinical stages taking into
account their strong points and their caveats. We covered strategies such as nucleosides analogs, oligonucleotides,
small molecule inhibitors, G-quadruplex stabilizers, immunotherapy, gene therapy, molecules that affect the telomere/
telomerase associated proteins, agents from microbial sources, among others, providing a balanced evaluation of the
status of the inhibitors of this powerful target together with an analysis of the challenges ahead.
