The Role of Telomerase in Cellular Stress Response—Therapeutic Potential of Telomerase Inhibitors

Cancer remains one of the most complex diseases and a major global problem. Current therapeutic strategies often fail because of severe side effects and insufficient selectivity. Thus, there is a need to identify novel, specific targets and personalized therapeutic approaches. Telomerase may be such a target. Although it has been studied primarily for its role in telomere maintenance and cellular immortality, its broader roles in cancer biology remain poorly understood. Many approaches targeting telomerase expression and activity focus on its primary function of restoring telomeres. However, studies show that the catalytic subunit of telomerase (TERT) shows additional functions that are independent of telomere restoration. These non-canonical functions support cancer cell survival, increased tolerance to cytotoxic stress, and enable tumor cells to adapt to adverse microenvironmental conditions. The mechanism by which non-canonical TERT functions in cellular stress responses (also due to therapeutic agents’ effects) remains unclear, and its therapeutic relevance is not yet fully understood. This review discusses the role of non-canonical telomerase functions in cancer cell stress responses and highlights the therapeutic potential of TERT/telomerase inhibition.