Telomerase: A prominent oncological target for development of chemotherapeutic agents

Telomerase is a ribonucleoprotein (RNP) responsible for the maintenance of chromosomal integrity by stabilizing telomere length. Telomerase is a widely expressed hallmark responsible for replicative immortality in 80-90% of malignant tumors. Cancer cells produce telomerase which prevents telomere shortening by adding telomeres sequences beyond Hayflick's limit; which enables them to divide uncontrollably. The activity of telomerase is relatively low in somatic cells and absent in normal cells, but the re-activation of this RNP in normal cells suppresses p53 activity which leads to the avoidance of senescence causing malignancy. Here, we have focused explicitly on various anti-telomerase therapies and telomerase-inhibiting molecules for the treatment of cancer. We have covered molecules that are reported in developmental, preclinical, and clinical trial stages as potent telomerase inhibitors. Apart from chemotherapy, we have also included details of immunotherapy, gene therapy, G-quadruplex stabilizers, and HSP-90 inhibitors. The purpose of this work is to discuss the challenges behind the development of novel telomerase inhibitors and to identify various perspectives for designing anti-telomerase compounds.

Automated summary

Telomerase is a ribonucleoprotein responsible for maintaining chromosome integrity. It is widely expressed in malignant tumors and prevents telomere shortening in cancer cells, promoting unlimited cell division. The re-activation of telomerase in normal cells suppresses p53 activity, leading to malignancy. This study focuses on anti-telomerase therapies and inhibitors, including chemotherapy, immunotherapy, gene therapy, G-quadruplex stabilizers, and HSP-90 inhibitors, to explore novel strategies for designing anti-telomerase compounds.