Telomerase and Regenerative Medicine
Calvin B. Harley
Geron Corporation, Menlo Park, CA, USA, 94301
There is now abundant experimental evidence in multiple human cell
types in culture for the causal relationships between telomere loss and
replicative senescence on one hand, and telomerase activation and
cellular immortalization on the other. These relationships are
supported by correlative data in human aging, chronic diseases, cancer,
experiments in telomerase knock-out mice, and human genetic conditions
of telomerase insufficiency. However, final, definitive data that
telomere biology plays a causal role in normal human aging and
age-related diseases, including cancer, will only come with specific
therapeutic intervention. We have worked on development of telomerase
vaccines, telomerase inhibitors, and telomerase promoter-driven cell
killing in oncology, and now have a therapeutic vaccine in the clinic,
and a telomerase antagonist in late preclinical studies. We are also
working on telomerase activation for a broad range of degenerative
diseases in which replicative senescence or telomere dysfunction may
play a role. Unfortunately, the strong link between telomerase and
cancer has led some to confuse telomerase activation with cancer, and
others to overstate the cancer risk of telomerase activation therapies
for degenerative diseases. This presentation will provide an update on
the status of telomerase-based cancer therapeutics, and review the data
that suggest transient telomerase activation may be a safe and
effective approach to regenerative medicine while reducing, rather than
increasing, the frequency of age-related tumorigenesis.
Key words:
telomerase, cancer, degenerative disease, telomere
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