Telomeres progressively shorten throughout life. A hallmark of advanced 
malignancies is the ability for continuous cell divisions that almost 
universally correlates with the stabilization of telomere length by the 
reactivation of telomerase. The repression of telomerase and shorter telomeres 
in humans may have evolved, in part, as an anticancer protection mechanism. 
Although there is still much we do not understand about the regulation of 
telomerase, it remains a very attractive and novel target for cancer 
therapeutics. This review focuses on the current state of advances in the 
telomerase area, identifies outstanding questions, and addresses areas and 
methods that need refinement.
SIGNIFICANCE: Despite many recent advances, telomerase remains a challenging 
target for cancer therapy. There are few telomerase-directed therapies, and many 
of the assays used to measure telomeres and telomerase have serious limitations. 
This review provides an overview of the current state of the field and how 
recent advances could affect future research and treatment approaches. Cancer 
Discov; 6(6); 584-93. ©2016 AACR.