Telomerase: Key regulator of inflammation and cancer

The telomerase holoenzyme, which has a highly conserved role in maintaining telomere length, has long been regarded as a high-profile target in cancer therapy due to the high dependency of the majority of cancer cells on constitutive and elevated telomerase activity for sustained proliferation and immortality. In this review, we present the salient findings in the telomerase field with special focus on the association of telomerase with inflammation and cancer. The elucidation of extra-telomeric roles of telomerase in inflammation, reactive oxygen species (ROS) generation, and cancer development further complicated the design of anti-telomerase therapy. Of note, the discovery of the unique mechanism that underlies reactivation of the dormant telomerase reverse transcriptase TERT promoter in somatic cells not only enhanced our understanding of the critical role of TERT in carcinogenesis but also opens up new intervention ideas that enable the differential targeting of cancer cells only. Despite significant effort invested in developing telomerase-targeted therapeutics, devising efficacious cancer-specific telomerase/TERT inhibitors remains an uphill task. The latest discoveries of the telomere-independent functionalities of telomerase in inflammation and cancer can help illuminate the path of developing specific anti-telomerase/TERT therapeutics against cancer cells.