Table 1. Outstanding Questions in the Telomere/Telomerase Field.

What are some of the outstanding questions in the telomere/telomerase field?

Telomerase (TERT) promoter mutations are considered the most common promoter point mutations in cancer. Are promoter mutations in TERT sufficient to activate telomerase and immortalize normal telomerase silent cells? Why do TERT promoter mutations occur in a tissue-specific manner? What are the mechanisms for telomerase activation in common tumor types that do not have TERT promoter mutations? How do most long-lived large mammals avoid cancer? Why do humans not follow other long-lived mammals in regard to reduced cancer incidence? Are the methods frequently used in cancer research for measuring telomerase and determining telomere length accurate? What are the strengths and weaknesses of these methods? How can they be improved? Why are there not more successful telomerase targeting approaches in cancer? Why have current approaches not progressed? What do we need to do to identify new approaches to targeting telomerase for cancer therapy that will be more effective?