Targeting telomerase for its advent in cancer therapeutics

Abstract

Telomerase has emerged as an important primary target in anticancer therapy. It is a distinctive reverse transcriptase enzyme, which extends the length of telomere at the 3′ chromosomal end, and uses telomerase reverse transcriptase (TERT) and telomerase RNA template‐containing domains. Telomerase has a vital role and is a contributing factor in human health, mainly affecting cell aging and cell proliferation. Due to its unique feature, it ensures unrestricted cell proliferation in malignancy and plays a major role in cancer disease. The development of telomerase inhibitors with increased specificity and better pharmacokinetics is being considered to design and develop newer potent anticancer agents. Use of natural and synthetic compounds for the inhibition of telomerase activity can lead to an opening of new vistas in cancer treatment. This review details about the telomerase biochemistry, use of natural and synthetic compounds; vaccines and oncolytic virus in therapy that suppress the telomerase activity. We have discussed structure‐activity relationships of various natural and synthetic telomerase inhibitors to help medicinal chemists and chemical biology researchers with a ready reference and updated status of their clinical trials. Suppression of human TERT (hTERT) activity through inhibition of hTERT promoter is an important approach for telomerase inhibition.

Oncolytic adenovirus promotes vascular normalization and nonclassical tertiary lymphoid structure formation through STING-mediated DC activation

“…Telomerase is usually highly expressed in tumor cells, but silent in normal cells. 51 Therefore, using the human telomerase reverse transcriptase (hTERT) promoter as the promoter of an OV can make the OV replicate specifically in tumor cells. 52 Deletion of the CR2 region of E1A and replacement with the hTERT promoter are two common ways to enhance the specific replication of an oncolytic adenovirus in cancer cells.…”

MAPK/ERK-CBP-RFPL-3 Mediates Adipose-Derived Stem Cell-Induced Tumor Growth in Breast Cancer Cells by Activating Telomerase Reverse Transcriptase Expression

“…Telomerase is involved in tumourigenesis-related signaling pathways in addition to telomere maintenance [ 27 ]. Telomerase reactivation or upregulation is governed by telomerase reverse transcriptase (TERT) expression [ 28 , 29 ].…”

Alternative Splicing of Human Telomerase Reverse Transcriptase (hTERT) and Its Implications in Physiological and Pathological Processes

“…Since functionally active hTERT enables replicative immortality of cancer cells and is silenced in adult somatic cells, it represents a suitable target for the development of highly selective therapeutics. To date, several classes of telomerase inhibitors were evaluated and demonstrated good toxic activity against cancer cells in vitro [ 171 ]. However, very few of them reported significant and reliable antitumor activity in clinical trials, as the efficacy of potential drug substances acting as telomerase inhibitors may be impaired for several reasons.…”