Combining old and new concepts in targeting telomerase for cancer therapy: transient, immediate, complete and combinatory attack (TICCA).

Telomerase can overcome replicative senescence by elongation of telomeres but is also a specific element in most cancer cells. It is expressed more vastly than any other tumor marker. Telomerase as a tumor target inducing replicative immortality can be overcome by only one other mechanism: alternative lengthening of telomeres (ALT). This limits the probability to develop resistance to treatments. Moreover, telomerase inhibition offers some degree of specificity with a low risk of toxicity in normal cells. Nevertheless, only one telomerase antagonist reached late preclinical studies. The underlying causes, the pitfalls of telomerase-based therapies, and future chances based on recent technical advancements are summarized in this review. Based on new findings and approaches, we propose a concept how long-term survival in telomerase-based cancer therapies can be significantly improved: the TICCA (Transient Immediate Complete and Combinatory Attack) strategy.