Target intelligence / Profile preview

Telomerase reverse transcriptase (hTERT) (hTERT)

Target
hTERT
Molecular classification
Enzyme, Reverse transcriptase, DNA-directed DNA polymerase
01

Overview

Telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase enzyme complex, which maintains chromosomal stability by adding telomeric repeats (TTAGGG) to the ends of chromosomes (UniProt O14746; NCBI Gene 7015). While hTERT expression is silenced in most adult somatic cells, it is reactivated in approximately 85-90% of human cancers, enabling the unlimited replicative potential characteristic of malignancy (Shay, J. W., 2016, Seminars in Cancer Biology). This near-universal expression in tumors compared to limited expression in normal tissues makes hTERT a primary target for anti-cancer therapies. Therapeutic interventions include telomerase inhibitors like imetelstat, which binds to the hTR RNA template to block catalytic activity, and various immunotherapies designed to recognize hTERT-derived peptides presented on the surface of cancer cells (Baerlocher et al., 2015, NEJM; Mizukoshi & Kaneko,}

Other names
TERThEST2TCS1TP2TRThTRTEST2Telomerase catalytic subunit
02

Mechanism of action

Direct inhibition of telomerase catalytic activity via competitive binding to the RNA template or induction of hTERT-specific cytotoxic T-lymphocyte responses through vaccination (Baerlocher et al., 2015, NEJM; Mizukoshi & Kaneko, 2019, Int J Mol Sci).

03

Biological functions

Telomere maintenanceCell immortalityDNA replicationRegulation of apoptosisSignal transduction
04

Disease associations

CancerDyskeratosis congenitaPulmonary fibrosisAplastic anemia
05

Safety considerations

Hematologic toxicity such as thrombocytopenia and neutropenia (Baerlocher et al., 2015, NEJM)Potential impairment of hematopoietic stem cell functionPotential effects on germ cell fertilityImmune-related adverse events from vaccines
06

Interacting drugs

Imetelstat

4 more in the full profile.

07

Biomarkers

hTERT mRNA expressionTelomerase activity (TRAP assay)Telomere length (Shay, J. W., 2016, Seminars in Cancer Biology)

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