Human telomerase reverse transcriptase (hTERT) (hTERT)

Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of the telomerase enzyme complex, which functions as a DNA polymerase to maintain telomere length by adding TTAGGG repeats to chromosome ends (UniProt O14746). While hTERT expression is repressed in most adult somatic cells, it is reactivated in approximately 90% of human malignancies, providing the replicative immortality necessary for tumor progression (PMID: 29959144). This high prevalence and tumor-specificity make hTERT a premier target for cancer therapy, particularly through the use of its antigenic epitopes in immunotherapy. Therapeutic strategies include peptide-based vaccines like GV1001 and UV1, which aim to elicit a T-cell mediated immune response against hTERT-positive cancer cells (PMID: 25103453). Additionally, direct inhibitors like the antisense oligonucleotide imetelstat target the telomerase RNA template to block enzymatic activity, leading to telomere shortening and cancer cell death (PMID: 26333180). Despite its promise, targeting hTERT requires careful management of potential toxicities in high-turnover tissues such as bone marrow (PMID: 30635449).

Other names

Telomerase reverse transcriptaseTERThEST2Telomerase catalytic subunitTCS1TP2TRTEST2

hTERT is targeted through two primary mechanisms: direct inhibition of its reverse transcriptase activity, which leads to progressive telomere shortening and replicative senescence, and immunotherapy, where antigenic epitopes of the hTERT protein are presented by MHC molecules to trigger a T-cell mediated attack on cancer cells (PMID: 26333180, PMID: 25103453).