Telomerase targeting as a therapeutic approach for sensitizing cancer cells to radiotherapy

Radiotherapy (RT) is recognized as one of the safest and most efficacious methods for combating cancer, with approximately 50% of patients diagnosed with solid tumors receiving ionizing radiation (IR) as part of their treatment. The therapeutic success of RT, however, is closely linked to the sensitivity of the tumor to radiation exposure. Various cancer types exhibit significant resistance to IR, which presents challenges in treatment. Thus, enhancing tumor cell sensitivity to IR could substantially improve patients' treatment outcomes and overall quality of life. Telomerase, a ribonucleoprotein holoenzyme, present in approximately 90% of cancers, plays a crucial role in maintaining telomere length (TL). Consequently, telomerase emerges as a prime target for intervention aimed at inhibiting the proliferation of cancer cells. An increase in telomerase activity is frequently associated with the uncontrolled cellular proliferation characteristic of cancer; numerous studies have established a direct link between telomerase activity and cellular radioresistance. Given the experimental evidence connecting telomere homeostasis to radiation sensitivity, targeting of telomerase is emerging as a promising strategy in cancer therapy, both as a standalone treatment and in conjunction with IR. In the present review article, we discuss the efficacy of telomerase targeting as a promising therapeutic strategy in promoting radiotherapy effect on various types of cancer.