Oligonucleotide-based
therapies have been under investigation for many years, and different antisense oligomers are being tested in clinical trials on patients with
cancer and other diseases. Since
telomerase reactivation has been defined as one of the six hallmarks of
cancer because of the
enzyme's ability to provide
tumor cells with unlimited proliferative potential, antisense-based approaches, aimed to inhibit the core
enzyme components, could represent innovative anticancer
therapies. Overall, available information indicates antisense-based strategies as powerful tools to inhibit
telomerase and interfere with
tumor cell proliferative potential. Specifically,
cancer cell growth arrest was observed in several
tumor models as a consequence of telomere shortening in the presence of prolonged
telomerase inhibition. However, in other studies, antisense-based treatments caused rapid loss of
tumor cell viability and induced apoptosis independently of telomere attrition. The results would suggest that
telomerase inhibition affects
tumor cell growth by mechanisms that are dependent as well as independent of the
enzyme telomere elongating activity. However, the role of
telomerase in
tumorigenesis and
tumor progression, beyond the classical mechanism of telomere lengthening, needs to be further investigated to provide a better rationale for the design and development of antitelomerase-based
therapies in clinical oncology.